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IMAI Toshio
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Research activity information

■ Paper
  • Atsushi Tanaka, Masanori Abe, Tadashi Namisaki, Shinji Shimoda, Mikio Zeniya, Akio Ido, Hitoshi Yoshiji, Hiromasa Ohira, Kenichi Harada, Yuko Kakuda, Atsushi Umeda, Yuki Kamiya, Yukari Higashine, Seiichiro Hojo, Toshio Imai, Tetsu Kawano, Yasuni Nakanuma, Hirohito Tsubouchi
    Jun. 2025, Journal of translational autoimmunity, 10, English
    Scientific journal

  • Jason W-L Eng, Yu Kato, Yusuke Adachi, Bhairavi Swaminathan, L A Naiche, Rahul Vadakath, Yoshimasa Sakamoto, Youya Nakazawa, Sho Tachino, Ken Ito, Takanori Abe, Yukinori Minoshima, Kana Hoshino-Negishi, Hideaki Ogasawara, Tomomi Kawakatsu, Miyuki Nishimura, Masahiko Katayama, Masashi Shimizu, Kazuhiro Tahara, Toshitaka Sato, Katsuhisa Suzuki, Kishan Agarwala, Masao Iwata, Kenichi Nomoto, Yoichi Ozawa, Toshio Imai, Yasuhiro Funahashi, Junji Matsui, Jan Kitajewski
    UNLABELLED: Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade can interfere with tumor vessel function but causes tissue hypoxia and gastrointestinal toxicity. Notch4 is primarily expressed in endothelial cells, where it may promote angiogenesis; however, effective therapeutic targeting of Notch4 has not been successful. We developed highly specific Notch4-blocking antibodies, 6-3-A6 and humanized E7011, allowing therapeutic targeting of Notch4 to be assessed in tumor models. Notch4 was expressed in tumor endothelial cells in multiple cancer models, and endothelial expression was associated with response to E7011/6-3-A6. Anti-Notch4 treatment significantly delayed tumor growth in mouse models of breast, skin, and lung cancers. Enhanced tumor inhibition occurred when anti-Notch4 treatment was used in combination with chemotherapeutics. Endothelial transcriptomic analysis of murine breast tumors treated with 6-3-A6 identified significant changes in pathways of vascular function but caused only modest change in canonical Notch signaling. Analysis of early and late treatment timepoints revealed significant differences in vessel area and perfusion in response to anti-Notch4 treatment. We conclude that targeting Notch4 improves tumor growth control through endothelial intrinsic mechanisms. SIGNIFICANCE: A first-in-class anti-Notch4 agent, E7011, demonstrates strong antitumor effects in murine tumor models including breast carcinoma. Endothelial Notch4 blockade reduces perfusion and vessel area.
    Jul. 2024, Cancer research communications, 4(7) (7), 1881 - 1893, English, International magazine
    Scientific journal

  • Takumi Hasegawa, Akira Utsunomiya, Takenao Chino, Hiroshi Kasamatsu, Tomomi Shimizu, Takashi Matsushita, Takashi Obara, Naoto Ishii, Hideaki Ogasawara, Wataru Ikeda, Toshio Imai, Noritaka Oyama, Minoru Hasegawa
    BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and inflammation, followed by excessive fibrosis of the skin and other internal organs, including the lungs. CX3CL1 (fractalkine), a chemokine expressed on endothelial cells, supports the migration of macrophages and T cells that express its specific receptor CX3CR1 into targeted tissues. We previously reported that anti-CX3CL1 monoclonal antibody (mAb) treatment significantly inhibited transforming growth factor (TGF)-β1-induced expression of type I collagen and fibronectin 1 in human dermal fibroblasts. Additionally, anti-mouse CX3CL1 mAb efficiently suppressed skin inflammation and fibrosis in bleomycin- and growth factor-induced SSc mouse models. However, further studies using different mouse models of the complex immunopathology of SSc are required before the initiation of a clinical trial of CX3CL1 inhibitors for human SSc. METHODS: To assess the preclinical utility and functional mechanism of anti-CX3CL1 mAb therapy in skin and lung fibrosis, a sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) mouse model was analyzed with immunohistochemical staining for characteristic infiltrating cells and RNA sequencing assays. RESULTS: On day 42 after bone marrow transplantation, Scl-cGVHD mice showed increased serum CX3CL1 level. Intraperitoneal administration of anti-CX3CL1 mAb inhibited the development of fibrosis in the skin and lungs of Scl-cGVHD model, and did not result in any apparent adverse events. The therapeutic effects were correlated with the number of tissue-infiltrating inflammatory cells and α-smooth muscle actin (α-SMA)-positive myofibroblasts. RNA sequencing analysis of the fibrotic skin demonstrated that cGVHD-dependent induction of gene sets associated with macrophage-related inflammation and fibrosis was significantly downregulated by mAb treatment. In the process of fibrosis, mAb treatment reduced cGVHD-induced infiltration of macrophages and T cells in the skin and lungs, especially those expressing CX3CR1. CONCLUSIONS: Together with our previous findings in other SSc mouse models, the current results indicated that anti-CX3CL1 mAb therapy could be a rational therapeutic approach for fibrotic disorders, such as human SSc and Scl-cGVHD.
    May 2024, Arthritis research & therapy, 26(1) (1), 94 - 94, English, International magazine
    Scientific journal

  • Shohei Abe, Atsuhiro Masuda, Tomonori Matsumoto, Jun Inoue, Hirochika Toyama, Arata Sakai, Takashi Kobayashi, Takeshi Tanaka, Masahiro Tsujimae, Kohei Yamakawa, Masanori Gonda, Shigeto Masuda, Hisahiro Uemura, Shinya Kohashi, Noriko Inomata, Kae Nagao, Yoshiyuki Harada, Mika Miki, Yosuke Irie, Noriko Juri, Testuhisa Ko, Yusuke Yokotani, Yuki Oka, Shogo Ota, Maki Kanzawa, Tomoo Itoh, Toshio Imai, Takumi Fukumoto, Eiji Hara, Yuzo Kodama
    BACKGROUND: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. METHODS: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. RESULTS: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. CONCLUSIONS: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.
    Mar. 2024, Journal of gastroenterology, 59(3) (3), 250 - 262, English, Domestic magazine
    Scientific journal

  • Shigeto Ashina, Atsuhiro Masuda, Kohei Yamakawa, Tsuyoshi Hamada, Masahiro Tsujimae, Takeshi Tanaka, Hirochika Toyama, Keitaro Sofue, Hideyuki Shiomi, Arata Sakai, Takashi Kobayashi, Shohei Abe, Masanori Gonda, Shigeto Masuda, Noriko Inomata, Hisahiro Uemura, Shinya Kohashi, Kae Nagao, Yoshiyuki Harada, Mika Miki, Noriko Juri, Yosuke Irie, Maki Kanzawa, Tomoo Itoh, Jun Inoue, Toshio Imai, Takumi Fukumoto, Yuzo Kodama
    BACKGROUND: Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. METHODS: We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis. RESULTS: Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41-12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08-4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59-3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36-5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34-6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). CONCLUSIONS: Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.
    Oct. 2023, Journal of gastroenterology, 58(10) (10), 1055 - 1067, English, Domestic magazine
    Scientific journal

  • Yoshikazu Kuboi#, Yuta Suzuki#, Sotaro Motoi# (#co-first authors), Chiyuki Matsui, Naoki Toritsuka, Tomoya Nakatani, Kazuhiro Tahara, Yoshinori Takahashi, Yoko Ida, Ayaka Tomimatsu, Motohiro Soejima, Toshio Imai
    Elsevier BV, Mar. 2023, Molecular Therapy - Nucleic Acids, 31, 339 - 351
    [Refereed]
    Scientific journal

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    OBJECTIVES: To evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis (RA) with an inadequate response to biological disease-modifying antirheumatic drugs (DMARDs). METHODS: In the double-blind treatment phase (24 weeks), placebo or E6011 400 mg was administered until week 10. Thereafter, E6011 200 mg or 400 mg was administered to week 22. Subjects who completed the evaluation at week 24 of the treatment phase were rolled over into the extension phase. The extension phase lasted until week 104, and all subjects received E6011 400 mg or 200 mg every 2 weeks in an open-label manner until week 102. RESULTS: A total of 47 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 46 (97.9%) subjects experienced any adverse events (AEs), and the incidence of treatment-related AEs was 57.4%. No clear efficacy trend in the American College of Rheumatology (ACR) 20 response rates were observed. CONCLUSIONS: E6011 was well tolerated in active RA patients who had shown an inadequate response to biologic DMARDs, but no clear benefit in the ACR20 response rates was observed. Further studies are needed to clarify the clinical benefit of E6011.
    Jan. 2023, Modern rheumatology, English, International magazine
    Scientific journal

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    OBJECTIVES: To evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). METHODS: Active RA patients with an inadequate response to MTX were randomly assigned to the E6011 or placebo group and received the study drug subcutaneously every 2 weeks during a 24-week double-blind study period. Subjects who completed evaluations at Week 24 were rolled over into the extension phase, and received open-label E6011 (200 mg or 400 mg) every 2 weeks until Week 102. The safety analysis was conducted up to Week 104, and the efficacy analysis was conducted up to Week 84. RESULTS: A total of 169 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 167 (98.8%) subjects experienced any adverse events (AEs), and the incidence of treatment-related AEs was 56.2%. The American College of Rheumatology (ACR) 20 response rates were observed between 40% and 70% during the extension phase. CONCLUSIONS: E6011 was safe and well-tolerated with no notable safety concerns up to 102 weeks in RA patients with an inadequate response to MTX.
    Jan. 2023, Modern rheumatology, English, International magazine
    Scientific journal

  • Shuntaro Tsukamoto, Naoko Hata Sugi, Kyoko Nishibata, Youya Nakazawa, Daisuke Ito, Sayo Fukushima, Takayuki Nakagawa, Kenji Ichikawa, Yu Kato, Dai Kakiuchi, Aya Goto, Machiko Itoh-Yagi, Tomoki Aota, Satoshi Inoue, Yoshinobu Yamane, Norio Murai, Hiroshi Azuma, Satoshi Nagao, Ken Sasai, Tsuyoshi Akagi, Toshio Imai, Junji Matsui, Tomohiro Matsushima
    Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-851, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemoresistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, cotreatment of ER-851 and antimitotic drugs produced an antitumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-851 is a promising candidate therapeutic agent for use against AXL-expressing antimitotic-resistant tumors.
    Jan. 2023, Molecular cancer therapeutics, 22(1) (1), 12 - 24, English, International magazine
    Scientific journal

  • Yoshikazu Kuboi, Yukiko Kuroda, Masayoshi Ohkuro, Sotaro Motoi, Yoshiya Tomimori, Hisataka Yasuda, Nobuyuki Yasuda, Toshio Imai, Koichi Matsuo
    Sep. 2022, JBMR Plus
    [Refereed]
    Scientific journal

  • Hidetoshi Ishigooka, Haruki Katsumata, Kan Saiga, Daisuke Tokita, Sotaro Motoi, Chiyuki Matsui, Yuta Suzuki, Ayaka Tomimatsu, Tomoya Nakatani, Yoshikazu Kuboi, Takafumi Yamakawa, Takashi Ikeda, Rumi Ishii, Toshio Imai, Toshio Takagi, Kazunari Tanabe
    BACKGROUND: Prophylaxis of antibody-mediated rejection (AMR) caused by donor-specific antibodies remains challenging. Given the critical roles of complement activity in antibody-mediated graft injury, we developed a lipid nanoparticle (LNP) formulation of small-interfering RNA against complement C5 (C5 siRNA-LNP) and investigated whether C5 siRNA-LNP could downregulate the complement activity and act as an effective treatment for AMR. METHODS: Lewis recipient rats were sensitized by skin grafting from Brown Norway donor rats. Kidney transplantation was performed at 4 wk post-skin grafting.C5 siRNA- or control siRNA-LNP was administered intravenously, and the weekly injections were continued until the study's conclusion. Cyclosporin (CsA) and/or deoxyspergualin (DSG) were used as adjunctive immunosuppressants. Complement activity was evaluated using hemolysis assays. The deposition of C5b9 in the grafts was evaluated using immunohistochemical analysis on day 7 posttransplantation. RESULTS: C5 siRNA-LNP completely suppressed C5 expression and complement activity (hemolytic activity ≤ 20%) 7 d postadministration. C5 siRNA-LNP in combination with CsA and DSG (median survival time: 56.0 d) prolonged graft survival compared with control siRNA-LNP in combination with CsA and DSG (median survival time: 21.0 d; P = 0.0012; log-rank test). Immunohistochemical analysis of the grafts revealed that downregulation of C5 expression was associated with a reduction in C5b9-positive area (P = 0.0141, Steel-Dwass test). CONCLUSIONS: C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
    Jun. 2022, Transplantation, English, International magazine
    Scientific journal

  • Taichi Kanzawa, Daisuke Tokita, Kan Saiga, Takafumi Yamakawa, Hidetoshi Ishigooka, Hironori Fukuda, Haruki Katsumata, Satoshi Miyairi, Rumi Ishii, Toshihito Hirai, Toshio Imai, Masayoshi Okumi, Kazunari Tanabe
    Transplantation outcomes are affected by the increase in rejection associated with ischemia reperfusion injury (IRI). Fractalkine (FKN), a chemokine for recruitment of CX3CR1+ leukocytes, contributes to the pathogenesis of various inflammatory diseases. Herein, we evaluated the importance of the FKN-CX3CR1 axis during IRI-related rejections using a mouse heterotopic heart transplantation model. FKN expression and graft survival was compared between wild-type C57BL/6 recipients transplanted with BALB/c hearts preserved for 8 (WT-IRI) and 0.5 h (WT-control) at 4°C. Graft survival of WT-IRI was shorter than that of WT-control. FKN was expressed on the vascular endothelium in WT-IRI allografts, but minimally in WT-control. The role of the FKN-CX3CR1 axis in IRI-related rejection was directly investigated using the transplant model with CX3CR1-deficient recipients (CX3CR1 KO-IRI) or treatment with anti-mouse FKN monoclonal antibodies. Graft survival of CX3CR1 KO-IRI was longer than that of WT-IRI; antibody treatment prolonged graft survival. The contribution of CX3CR1+ monocytes to IRI-related rejection was evaluated by adoptive transfer to CX3CR1 KO-IRI. Adoptive transfer of CX3CR1+ monocytes attenuated the effect of prolonged graft survival in CX3CR1 KO-IRI. Overall, the FKN-CX3CR1 axis plays a major role during IRI-related rejection; its blockade has the potential to improve the outcomes of deceased donor transplantation.
    2022, Transplant international : official journal of the European Society for Organ Transplantation, 35, 10157 - 10157, English, International magazine
    Scientific journal

  • Katsuyoshi Matsuoka, Makoto Naganuma, Toshifumi Hibi, Hirohito Tsubouchi, Kiyoshi Oketani, Toshinori Katsurabara, Seiichiro Hojo, Osamu Takenaka, Tetsu Kawano, Toshio Imai, Takanori Kanai
    Aug. 2021, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 36(8) (8), 2180 - 2186, English, International magazine
    Scientific journal

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Jul. 2021, Modern rheumatology, 31(4) (4), 783 - 789, English, International magazine
    Scientific journal

  • Sotaro Motoi, Mai Uesugi, Takashi Obara, Katsuhiro Moriya, Yoshihisa Arita, Hideaki Ogasawara, Motohiro Soejima, Toshio Imai, Tetsu Kawano
    May 2021, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(9) (9), English
    Scientific journal

  • Satoshi Mizutani, Junko Nishio, Kanoh Kondo, Kaori Motomura, Zento Yamada, Shotaro Masuoka, Soichi Yamada, Sei Muraoka, Naoto Ishii, Yoshikazu Kuboi, Sho Sendo, Tetuo Mikami, Toshio Imai, Toshihiro Nanki
    May 2021, PHARMACEUTICALS, 14(5) (5), English, International magazine
    Scientific journal

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Apr. 2021, ARTHRITIS & RHEUMATOLOGY, 73(4) (4), 587 - 595, English
    Scientific journal

  • Tomoko Watanabe, Jungo Kakuta, Sayoko Saito, Kayo Hasehira, Kayo Kiyoi, Toshio Imai, Hiroaki Tateno
    Elsevier BV, Nov. 2020, Biochemical and Biophysical Research Communications, 532(4) (4), 647 - 654
    Scientific journal

  • Sei Muraoka, Junko Nishio, Yoshikazu Kuboi, Toshio Imai, Toshihiro Nanki
    Nov. 2020, EXPERT OPINION ON BIOLOGICAL THERAPY, 20(11) (11), 1309 - 1319, English, International magazine
    Scientific journal

  • Soichi Yamada, Shion Miyoshi, Junko Nishio, Satoshi Mizutani, Zento Yamada, Natsuko Kusunoki, Hiroshi Sato, Yoshikazu Kuboi, Kana Hoshino-Negishi, Naoto Ishii, Toshio Imai, Tetsuo Mikami, Hiroyasu Nakano, Shinichi Kawai, Toshihiro Nanki
    Sep. 2020, EUROPEAN JOURNAL OF INFLAMMATION, 18, English
    Scientific journal

  • Yoshiya Tanaka, Kana Hoshino-Negishi, Yoshikazu Kuboi, Fumitoshi Tago, Nobuyuki Yasuda, Toshio Imai
    2020, IMMUNOTARGETS AND THERAPY, 9, 241 - 253, English, International magazine
    Scientific journal

  • Vu H. Luong, Akira Utsunomiya, Takenao Chino, Le H. Doanh, Takashi Matsushita, Takashi Obara, Yoshikazu Kuboi, Naoto Ishii, Akihito Machinaga, Hideaki Ogasawara, Wataru Ikeda, Tetsu Kawano, Toshio Imai, Noritaka Oyama, Minoru Hasegawa
    Nov. 2019, ARTHRITIS & RHEUMATOLOGY, 71(11) (11), 1923 - 1934, English, International magazine
    Scientific journal

  • EFFICACY AND SAFETY OF E6011, ANTI-HUMAN FRACTALKINE MONOCLONAL ANTIBODY, IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS WITH AN INCOMPLETE RESPONSE TO URSODEOXYCHOLIC ACID : A PLACEBO-CONTROLLED DOUBLE-BLIND COMPARISON PHASE 2 STUDY.
    Atsushi Tanaka, Masanori Abe, Tadashi Namisaki, Shinji Shimoda, Mikio Zeniya, Akio Ido, Hitoshi Yoshiji, Hiromasa Ohira, Kenichi Harada, Yuko Kakuda, Atsushi Umeda, Yuki Kamiya, Yukari Higashine, Seiichiro Hojo, Toshio Imai, Tetsu Kawano, Yasuni Nakanuma, Hirohito Tsubouchi
    Oct. 2019, HEPATOLOGY, 70, 767A - 767A, English

  • A Phase 2 Study of E6011, an Anti-Fractalkine Monoclonal Antibody, in Patients with Rheumatoid Arthritis Inadequately Responding to Biologics
    Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Hayato Hisaki, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Oct. 2019, ARTHRITIS & RHEUMATOLOGY, 71, English

  • Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in MTX-IR Patients with Rheumatoid Arthritis
    Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Oct. 2019, ARTHRITIS & RHEUMATOLOGY, 71, English

  • Immuno-Phenotypic Analysis of Peripheral Blood Mononuclear Cells in Rheumatoid Arthritis Patients Treated with E6011, a Humanized Anti-Fractalkine Monoclonal Antibody
    Tomohiro Yamada, Jungo Kakuta, Eri Fusaoka-Nishioka, Jun-ichi Ito, Nobuyuki Yasuda, Tetsu Kawano, Toshio Imai
    Oct. 2019, ARTHRITIS & RHEUMATOLOGY, 71, English

  • Naoto Ishii, Kana Hoshino-Negishi, Masayoshi Ohkuro, Tomoya Nakatani, Wataru Ikeda, Yoshikazu Kuboi, Nobuyuki Yasuda, Toshio Imai
    Jun. 2019, ANNALS OF THE RHEUMATIC DISEASES, 78, 1087 - 1088, English

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Hayato Hisaki, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Jun. 2019, ANNALS OF THE RHEUMATIC DISEASES, 78, 1131 - 1132, English

  • Soichi Yamada, Shion Miyoshi, Natsuko Kusunoki, Hiroshi Sato, Yoshikazu Kuboi, Kana Hoshino-Negishi, Naoto Ishii, Toshio Imai, Tetsuo Mikami, Hiroyasu Nakano, Shinichi Kawai, Toshihiro Nanki
    Jun. 2019, ANNALS OF THE RHEUMATIC DISEASES, 78, 295 - 295, English

  • Yoshikazu Kuboi, Miyuki Nishimura, Wataru Ikeda, Tomoya Nakatani, Yukie Seki, Yui Yamaura, Kana Ogawa, Akiko Hamaguchi, Kenzo Muramoto, Keiko Mizuno, Hideaki Ogasawara, Toshihiko Yamauchi, Nobuyuki Yasuda, Hiroshi Onodera, Toshio Imai
    May 2019, INTERNATIONAL IMMUNOLOGY, 31(5) (5), 357 - 357, English

  • Yoshikazu Kuboi, Miyuki Nishimura, Wataru Ikeda, Tomoya Nakatani, Yukie Seki, Yui Yamaura, Kana Ogawa, Akiko Hamaguchi, Kenzo Muramoto, Keiko Mizuno, Hideaki Ogasawara, Toshihiko Yamauchi, Nobuyuki Yasuda, Hiroshi Onodera, Toshio Imai
    May 2019, INTERNATIONAL IMMUNOLOGY, 31(5) (5), 287 - 302, English, International magazine
    Scientific journal

  • Hiroko Tabuchi, Toshinori Katsurabara, Masahiko Mori, Muneo Aoyama, Takashi Obara, Nobuyuki Yasuda, Tetsu Kawano, Toshio Imai, Ichiro Ieiri, Yuji Kumagai
    May 2019, JOURNAL OF CLINICAL PHARMACOLOGY, 59(5) (5), 688 - 701, English, International magazine
    Scientific journal

  • Yoshikazu Kuboi, Miyuki Nishimura, Wataru Ikeda, Tomoya Nakatani, Yukie Seki, Yui Yamaura, Kana Ogawa, Akiko Hamaguchi, Kenzo Muramoto, Keiko Mizuno, Hideaki Ogasawara, Toshihiko Yamauchi, Nobuyuki Yasuda, Hiroshi Onodera, Toshio Imai
    Oxford University Press, Apr. 2019, International Immunology, 31(5) (5), 287 - 302, English
    Scientific journal

  • Sotaro Motoi, Hiroko Toyoda, Takashi Obara, Etsuko Ohta, Yoshihisa Arita, Kana Negishi, Katsuhiro Moriya, Yoshikazu Kuboi, Motohiro Soejima, Toshio Imai, Akio Ido, Hirohito Tsubouchi, Tetsu Kawano
    Apr. 2019, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(8) (8), English
    Scientific journal

  • Kana Hoshino-Negishi, Masayoshi Ohkuro, Tomoya Nakatani, Yoshikazu Kuboi, Miyuki Nishimura, Yoko Ida, Jungo Kakuta, Akiko Hamaguchi, Minoru Kumai, Tsutomu Kamisako, Fumihiro Sugiyama, Wataru Ikeda, Naoto Ishii, Nobuyuki Yasuda, Toshio Imai
    Feb. 2019, Arthritis & rheumatology (Hoboken, N.J.), 71(2) (2), 222 - 231, English, International magazine
    Scientific journal

  • Naoki Morita, Eiji Umemoto, Setsuko Fujita, Akio Hayashi, Junichi Kikuta, Ikuo Kimura, Takeshi Haneda, Toshio Imai, Asuka Inoue, Hitomi Mimuro, Yuichi Maeda, Hisako Kayama, Ryu Okumura, Junken Aoki, Nobuhiko Okada, Toshiyuki Kida, Masaru Ishii, Ryusuke Nabeshima, Kiyoshi Takeda
    Feb. 2019, Nature, 566(7742) (7742), 110 - 114, English, International magazine
    Scientific journal

  • Anti-Fractalkine Monoclonal Antibody Inhibits Joint Destruction through Suppression of Osteoclast Precursor Migration and Induces Synovial Cell Death in Collagen-Induced Arthritis Model Mice
    Kana Hoshino-Negishi, Masayoshi Ohkuro, Tomoya Nakatani, Wataru Ikeda, Yoshikazu Kuboi, Naoto Ishii, Nobuyuki Yasuda, Toshio Imai
    Sep. 2018, ARTHRITIS & RHEUMATOLOGY, 70, English

  • Anti-Fractalkine Monoclonal Antibody Dislodges Intravascular Monocytes Involved in Exacerbation of Synovial Inflammation in Collagen-Induced Arthritis Model
    Wataru Ikeda, Kana Hoshino-Negishi, Eri Fusaoka-Nishioka, Tomoya Nakatani, Yoshikazu Kuboi, Naoto Ishii, Nobuyuki Yasuda, Toshio Imai
    Sep. 2018, ARTHRITIS & RHEUMATOLOGY, 70, English

  • MULTIPLE ASCENDING DOSE, OPEN-LABEL, PHASE 1/2 STUDY OF E6011, AN ANTI-FRACTALKINE MONOCLONAL ANTIBODY, TO INVESTIGATE THE SAFETY AND CLINICAL RESPONSE IN PATIENTS WITH CROHN'S DISEASE
    Satoshi Tanida, Katsuyoshi Matsuoka, Makoto Naganuma, Kazuya Kitamura, Toshiyuki Matsui, Makoto Arai, Mikihiro Fujiya, Noriyuki Horiki, Hiroko Nebiki, Fukunori Kinjo, Takako Miyazaki, Takayuki Matsumoto, Motohiro Esaki, Keiichi Mitsuyama, Masayuki Saruta, Akio Ido, Seiichiro Hojo, Osamu Takenaka, Kiyoshi Oketani, Toshio Imai, Hirohito Tsubouchi, Toshifumi Hibi, Takanori Kanai
    May 2018, GASTROENTEROLOGY, 154(6) (6), S830 - S830, English

  • Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Yasumi Kitahara, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    2018, MODERN RHEUMATOLOGY, 28(1) (1), 58 - 65, English, International magazine
    Scientific journal

  • Anti-CX3CL1 monoclonal antibody therapy suppresses the development of bleomycin-induced and growth factors-induced skin fibrosis in mice
    Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Obara, Yoshikazu Kuboi, Naoto Ishii, Akihito Machinaga, Hideaki Ogasawara, Wataru Ikeda, Toshio Imai, Minoru Hasegawa
    Dec. 2017, CYTOKINE, 100, 44 - 44, English

  • Hiroshi Sato, Sei Muraoka, Natsuko Kusunoki, Shotaro Masuoka, Soichi Yamada, Hideaki Ogasawara, Toshio Imai, Yoshikiyo Akasaka, Naobumi Tochigi, Hiroshi Takahashi, Kazuaki Tsuchiya, Shinichi Kawai, Toshihiro Nanki
    Dec. 2017, ARTHRITIS RESEARCH & THERAPY, 19(1) (1), 263 - 263, English, International magazine
    Scientific journal

  • Hisashi Wakita, Tatsuya Yanagawa, Yoshikazu Kuboi, Toshio Imai
    Nov. 2017, MOLECULAR PHARMACOLOGY, 92(5) (5), 502 - 509, English, International magazine
    Scientific journal

  • Anti-Fractalkine Monoclonal Antibody Ameliorates Joint Destruction in Collagen-Induced Arthritis Model through Suppression of Osteoclast Precursor Cell Survival and Migration
    Yoshikazu Kuboi, Kana Hoshino-Negishi, Masayoshi Ohkuro, Wataru Ikeda, Tomoya Nakatani, Naoto Ishii, Toshihiko Yamauchi, Nobuyuki Yasuda, Toshio Imai
    Oct. 2017, ARTHRITIS & RHEUMATOLOGY, 69, English

  • Safety, Pharmacokinetics, and Efficacy of E6011, an Anti-Fractalkine Monoclonal Antibody, in a First-in-Patient Phase 1/2 Study on Rheumatoid Arthritis: 52-Week Results
    Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Yasumi Kitahara, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Oct. 2017, ARTHRITIS & RHEUMATOLOGY, 69, English

  • Fractalkine mediated locally accumulated CX3CR1(+) macrophages recruit iNOS(+) macrophages and neutrophils by production of MCP-1 chemokine to lead immune mediated hepatitis
    Miyuki Nishimura, Yoshikazu Kuboi, Kenzo Muramoto, Keiko Mizuno, Hideaki Ogasawara, Toshihiko Yamauchi, Nobuyuki Yasuda, Toshio Imai
    Oct. 2017, HEPATOLOGY, 66, 152A - 152A, English

  • Stimulation with Resistin Upregulates Chemokine Production By Fibroblast-like Synoviocytes from Patients with Rheumtoid Arthritis
    Hiroshi Sato, Sei Muraoka, Natsuko Kusunoki, Shotaro Masuoka, Soichi Yamada, Toshio Imai, Shinichi Kawai, Toshihiro Nanki
    Oct. 2017, ARTHRITIS & RHEUMATOLOGY, 69, English

  • Toshihiro Nanki, Toshio Imai, Shinichi Kawai
    2017, MODERN RHEUMATOLOGY, 27(3) (3), 392 - 397, English, International magazine
    Scientific journal

  • Chie Kojima, Eri Fusaoka-Nishioka, Toshio Imai, Atsushi Nakahira, Hiroshi Onodera
    Poly(glycolic acid) (PGA) fibers are a good candidate material for nerve cell scaffolds, which is applicable to the treatment of peripheral nerve injuries. Polylysine is widely used as a coating material for cell substrates to promote nerve cell adhesion. In this study, linear and dendrigraft polylysines were used to coat PGA fibers. The association of large dendrigraft polylysines with PGA fibers was lower and unstable, compared with linear polylysine. However, more hippocampal neurons adhered to PGA fibers coated with large dendrigraft polylysine than linear polylysine. Enhanced cell adhesion was observed, even when the dendrigraft polylysine was coated on the PGA fibers at a low concentration (0.05 μg/mL) or when it was coated in water instead of alkaline buffer. Differences in cell adhesion properties were seen between the dendrigraft polylysine coating and a laminin coating. Thus, large dendrigraft polylysines are a useful coating material for nerve cell scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2744-2750, 2016.
    Nov. 2016, Journal of biomedical materials research. Part A, 104(11) (11), 2744 - 50, English, International magazine
    Scientific journal

  • Anti-Fractalkine Monoclonal Antibody Inhibits Cartilage Destruction and Bone Erosion in Collagen-Induced Arthritis Model
    Kana Hoshino, Masayoshi Ohkuro, Wataru Ikeda, Tomoya Nakatani, Yoshikazu Kuboi, Naoto Ishii, Toshihiko Yamauchi, Nobuyuki Yasuda, Toshio Imai
    Oct. 2016, ARTHRITIS & RHEUMATOLOGY, 68, English

  • Katsuyoshi Matsuoka, Makoto Naganuma, Toshiyuki Matsui, Makoto Arai, Satoshi Tanida, Kazuya Kitamura, Noriyuki Horiki, Mikihiro Fujiya, Masaki Iimuro, Keiichi Mitsuyama, Masayuki Saruta, Takayuki Matsumoto, Hiroko Nebiki, Motohiro Esaki, Fukunori Kinjo, Kiyoshi Oketani, Seiichiro Hojo, Hideto Akama, Toshio Imai, Hirohito Tsubouchi, Toshifumi Hibi, Takanori Kanai
    Apr. 2016, GASTROENTEROLOGY, 150(4) (4), S808 - S808, English

  • Toshio Imai, Nobuyuki Yasuda
    2016, INFLAMMATION AND REGENERATION, 36, 9 - 9, English, International magazine
    Scientific journal

  • Safety and Efficacy of E6011, an Anti-Fractalkine Monoclonal Antibody, in a First-in-Patient Phase 1/2 Study in Rheumatoid Arthritis
    Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Hideto Akama, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
    Oct. 2015, ARTHRITIS & RHEUMATOLOGY, 67, English

  • Advanced In Vivo Live Imaging of Vascular Network of Colon Submucosa in IBD Models Using Two-Photon Laser Microscopy
    Wataru Ikeda, Akiko Hamaguchi, Yoshihisa Arita, Yoshikazu Kuboi, Kenzo Muramoto, Toshio Imai
    Apr. 2015, GASTROENTEROLOGY, 148(4) (4), S224 - S224, English

  • Inflammation via the Fractalkine (CX3CL1)/CX3CR1 Pathway Is Distinct From the TNF Pathway in Murine Colitis Model
    Sotaro Motoi, Masayoshi Ohkuro, Wataru Ikeda, Akiko Hamaguchi, Kenzo Muramoto, Toshitaka Sato, Nobuyuki Yasuda, Akiharu Kajiwara, Tetsu Kawano, Toshio Imai
    Apr. 2015, GASTROENTEROLOGY, 148(4) (4), S684 - S684, English

  • Yoshihiro Kitagawa, Shojiro Kikuchi, Yoshihisa Arita, Miyuki Nishimura, Keiko Mizuno, Hideaki Ogasawara, Tetsu Kawano, Toshiya Ochiai, Eigo Otsuji, Toshio Imai
    Jul. 2013, SURGERY, 154(1) (1), 78 - 88, English, International magazine
    Scientific journal

  • Akiyoshi Hoshino, Satoshi Ueha, Sanshiro Hanada, Toshio Imai, Masako Ito, Kenji Yamamoto, Kouji Matsushima, Akira Yamaguchi, Tadahiro Iimura
    Feb. 2013, JOURNAL OF CELL SCIENCE, 126(4) (4), 1032 - 1045, English, International magazine
    Scientific journal

  • Michinori Kitagawa, Atsushi Takebe, Yuichi Ono, Toshio Imai, Kazuki Nakao, Shin-Ichi Nishikawa, Takumi Era
    Aug. 2012, JOURNAL OF BIOLOGICAL CHEMISTRY, 287(33) (33), 27983 - 27996, English
    Scientific journal

  • Fumihito Suzuki, Tetsuo Kubota, Yasunari Miyazaki, Kinya Ishikawa, Masashi Ebisawa, Shunsei Hirohata, Takashi Ogura, Hidehiro Mizusawa, Toshio Imai, Nobuyuki Miyasaka, Toshihiro Nanki
    Mar. 2012, Arthritis research & therapy, 14(2) (2), R48, English, International magazine
    Scientific journal

  • Eri Fusaoka-Nishioka, Chisei Shimono, Yukimasa Taniguchi, Aki Togawa, Akio Yamada, Eiji Inoue, Hiroshi Onodera, Kiyotoshi Sekiguchi, Toshio Imai
    Dec. 2011, Neuroscience research, 71(4) (4), 421 - 6, English, International magazine
    Scientific journal

  • Chemerin Activates Fibroblast-Like Synoviocytes In Patients with Rheumatoid Arthritis.
    Kayoko Kaneko, Yoshishige Miyabe, Aiko Takayasu, Shin Fukuda, Chie Miyabe, Masashi Ebisawa, Waka Yokoyama, Kaori Watanabe, Toshio Imai, Kenzo Muramoto, Yuya Terashima, Takahiko Sugihara, Kouji Matsushima, Nobuyuki Miyasaka, Toshihiro Nanki
    Oct. 2011, ARTHRITIS AND RHEUMATISM, 63(10) (10), S140 - S140, English

  • Daiji Kiyozumi, Aki Osada, Nagisa Sugimoto, Charles N. Weber, Yuichi Ono, Toshio Imai, Akiko Okada, Kiyotoshi Sekiguchi
    Jul. 2011, Journal of Dermatology, 38(7) (7), 674 - 679
    Scientific journal

  • Kenta Takashima, Eri Nishioka, Masato Hoshino, Kentaro Uesugi, Naoto Yagi, Toshio Imai, Atsushi Nakahira, Masahiro Kohzuki, Noriko Osumi, Hiroshi Onodera
    2011, NEUROSCIENCE RESEARCH, 71, E308 - E308, English

  • Kayoko Kaneko, Yoshishige Miyabe, Aiko Takayasu, Shin Fukuda, Chie Miyabe, Masashi Ebisawa, Waka Yokoyama, Kaori Watanabe, Toshio Imai, Kenzo Muramoto, Yuya Terashima, Takahiko Sugihara, Kouji Matsushima, Nobuyuki Miyasaka, Toshihiro Nanki
    2011, ARTHRITIS RESEARCH & THERAPY, 13(5) (5), R158, English, International magazine
    Scientific journal

  • Tomoyuki Tagi, Takeshi Matsui, Shojiro Kikuchi, Sachi Hoshi, Toshiya Ochiai, Yukihito Kokuba, Yoko Kinoshita-Ida, Fumie Kisumi-Hayashi, Koji Morimoto, Toshio Imai, Issei Imoto, Johji Inazawa, Eigo Otsuji
    Dec. 2010, JOURNAL OF GASTROENTEROLOGY, 45(12) (12), 1201 - 1211, English
    Scientific journal

  • The fractalkine/CX3CR1 pathway is involved in the development of symptoms and allodynia in EAE through distinct mechanisms, and has both peripheral and central roles
    Muramoto Kenzo, Imai Toshio, Nishimura Miyuki, Kumai Minoru, Yanagawa Tatsuya
    Nov. 2010, JOURNAL OF NEUROIMMUNOLOGY, 228(1-2) (1-2), 46 - 47, English

  • Akiyoshi Hoshino, Tadahiro Iimura, Satoshi Ueha, Sanshiro Hanada, Yutaka Maruoka, Mitsuori Mayahara, Keiko Suzuki, Toshio Imai, Masako Ito, Yoshinobu Manome, Masato Yasuhara, Takaaki Kirino, Akira Yamaguchi, Kouji Matsushima, Kenji Yamamoto
    Sep. 2010, JOURNAL OF BIOLOGICAL CHEMISTRY, 285(37) (37), 28826 - 28837, English, International magazine
    Scientific journal

  • Keiichi Koizumi, Yurika Saitoh, Takayuki Minami, Nobuhiro Takeno, Koichi Tsuneyama, Tatsuro Miyahara, Takashi Nakayama, Hiroaki Sakurai, Yasuo Takano, Miyuki Nishimura, Toshio Imai, Osamu Yoshie, Ikuo Saiki
    Dec. 2009, JOURNAL OF IMMUNOLOGY, 183(12) (12), 7825 - 7831, English, International magazine
    Scientific journal

  • Miyuki Nishimura, Yoshikazu Kuboi, Kenzo Muramoto, Tetsu Kawano, Toshio Imai
    2009, CONTEMPORARY CHALLENGES IN AUTOIMMUNITY, 1173, 350 - 356, English, International magazine
    Scientific journal

  • The pathway of CX3CR1 and fractalkine interaction is involved in the leukocytes infiltration on experimental autoimmune encephalomyelitis in mice
    Kenzo Muramoto, Yoshikazu Kuboi, Hideaki Ogasawara, Etsuko Rikitsli, Keiko Mizuno, Miyuki Nishimura, Toshio Imai
    Oct. 2008, JOURNAL OF NEUROIMMUNOLOGY, 203(2) (2), 256 - 256, English

  • Fiona E. Holmes, Nighat Arnott, Penny Vanderplank, Niall C. H. Kerr, Erin E. Longbrake, Philip G. Popovich, Toshio Imai, Christophe Combadiere, Philip M. Murphy, David Wynick
    Jul. 2008, JOURNAL OF NEUROCHEMISTRY, 106(2) (2), 640 - 649, English, International magazine
    Scientific journal

  • K. Morimoto, K. Satoh-Yamaguchi, A. Hamaguchi, Y. Inoue, M. Takeuchi, M. Okada, W. Ikeda, Y. Takai, T. Imai
    Jan. 2008, ONCOGENE, 27(3) (3), 264 - 273, English
    Scientific journal

  • Noriko Mizutani, Toshiharu Sakurai, Takahiro Shibata, Koji Uchida, Jun Fujita, Rei Kawashima, Yuki I. Kawamura, Noriko Toyama-Sorimachi, Toshio Imai, Taeko Dohi
    Dec. 2007, JOURNAL OF IMMUNOLOGY, 179(11) (11), 7478 - 7487, English, International magazine
    Scientific journal

  • Yuichi Ono, Tomoya Nakatani, Yoshimasa Sakamoto, Eri Mizuhara, Yasuko Minaki, Minoru Kumai, Akiko Hamaguchi, Miyuki Nishimura, Yoko Inoue, Hideki HayashiO, Jun Takahashi, Toshio Imai
    Sep. 2007, DEVELOPMENT, 134(17) (17), 3213 - 3225, English
    Scientific journal

  • Taku Kobayashi, Susumu Okamoto, Yuko Iwakami, Atsushi Nakazawa, Tadakazu Hisamatsu, Hiroshi Chinen, Nobuhiko Kamada, Toshio Imai, Hidemi Goto, Toshifumi Hibi
    Jul. 2007, INFLAMMATORY BOWEL DISEASES, 13(7) (7), 837 - 846, English, International magazine
    Scientific journal

  • Fractalkine regulates TNF-alpha secretion by macrophages with induction of eperoxisome proliferator-activated receptor-gamma and its ligand
    Noriko Mizorai, Toshiharu Sakurai, Iakahiro Shibata, Koji Uchida, Jun Fujita, Rei Kawashima, Yuki I. Kawamura, Noriko Toyama-sorimachi, Toshio Imai, Taeko Dohi
    Apr. 2007, GASTROENTEROLOGY, 132(4) (4), A707 - A708, English

  • Yuko Sugihara-Mizuno, Makoto Adachi, Yuka Kobayashi, Yoko Hamazaki, Miyuki Nishimura, Toshio Imai, Mikio Furuse, Shoichiro Tsukita
    Apr. 2007, GENES TO CELLS, 12(4) (4), 473 - 486, English
    Scientific journal

  • Satoshi Ueha, Masako Murai, Hiroyuki Yoneyama, Masahiro Kitabatake, Toshio Imai, Takeshi Shimaoka, Shin Yonehara, Sho Ishikawa, Kouji Matsushima
    Jan. 2007, JOURNAL OF LEUKOCYTE BIOLOGY, 81(1) (1), 176 - 185, English, International magazine
    Scientific journal

  • Hiroyoshi Ishizaki, Atsushi Togawa, Miki Tanaka-Okamoto, Keiko Hori, Miyuki Nishimura, Akiko Hamaguchi, Toshio Imai, Yoshimi Takai, Jun Miyoshi
    Dec. 2006, JOURNAL OF IMMUNOLOGY, 177(12) (12), 8512 - 8521, English, International magazine
    Scientific journal

  • Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand expressed on a subset of skin-homing helper memory T cells.
    Katsuyuki Ohmori, Fumiyo Fukui, Makoto Kiso, Toshio Imai, Osamu Yoshie, Hitoshi Hasegawa, Kouji Matsushima, Reiji Kannagi
    We previously identified the carbohydrate determinant sialyl 6-sulfo Lewis X (Le(x)) as the major L-selectin ligand on high endothelial venules of peripheral lymph nodes. In this study, we examined the distribution of the sialyl 6-sulfo Le(x) determinant among peripheral lymphocytes. The determinant was expressed on a subset of helper memory T and NK cells. The helper memory T cells expressing sialyl 6-sulfo Le(x) were CD45RO(bright+) PSGL-1(high+) CCR4+ L-selectin+ CCR7+ but did not express alpha4beta7 integrin or CCR9, indicating that they were the skin-homing population of central memory T cells. The T-cell subset significantly expressed mRNA for 6-sulfotransferase HEC-GlcNAc6ST and fucosyltransferase Fuc-T VII, responsible for the synthesis of sialyl 6-sulfo Le(x). Characteristics of the T-cell population were similar to those previously described for cutaneous lymphocyte-associated antigen (CLA)-positive T cells defined by the HECA-452 or 2F3 antibody. The binding of the T-cell subset with the specific anti-sialyl 6-sulfo Le(x) antibody G152 was almost completely abrogated by HECA-452 or 2F3. Binding of recombinant E-, P-, and L-selectins to the T-cell subset was significantly inhibited by G152 and by HECA-452 antibodies. We propose that CLA, which is expressed without any activation stimuli on peripheral skin-homing helper memory T cells in healthy persons, is at least partly the sialyl 6-sulfo Le(x) determinant.
    Apr. 2006, Blood, 107(8) (8), 3197 - 204, English, International magazine
    Scientific journal

  • Fractalkine and its receptor CX3CR1 are upregulated in inflammatory bowel disease
    Taku Kobayashi, Susumu Okamoto, Yuko Iwakami, Atsushi Nakazawa, Tadakazu Hisamatsu, Toshio Imai, Toshfumi Hibi
    Apr. 2006, GASTROENTEROLOGY, 130(4) (4), A355 - A355, English

  • Inhibition of CX3CL1 (fractalkine) improves experimental autoimmune myositis in SJL/J mice.
    Fumihito Suzuki, Toshihiro Nanki, Toshio Imai, Hirotoshi Kikuchi, Shunsei Hirohata, Hitoshi Kohsaka, Nobuyuki Miyasaka
    Idiopathic inflammatory myopathy is a chronic inflammatory muscle disease characterized by mononuclear cell infiltration in the skeletal muscle. The infiltrated inflammatory cells express various cytokines and cytotoxic molecules. Chemokines are thought to contribute to the inflammatory cell migration into the muscle. We induced experimental autoimmune myositis (EAM) in SJL/J mice by immunization with rabbit myosin and CFA. In the affected muscles of EAM mice, CX3CL1 (fractalkine) was expressed on the infiltrated mononuclear cells and endothelial cells, and its corresponding receptor, CX3CR1, was expressed on the infiltrated CD4 and CD8 T cells and macrophages. Treatment of EAM mice with anti-CX3CL1 mAb significantly reduced the histopathological myositis score, the number of necrotic muscle fibers, and infiltration of CD4 and CD8 T cells and macrophages. Furthermore, treatment with anti-CX3CL1 mAb down-regulated the mRNA expression of TNF-alpha, IFN-gamma, and perforin in the muscles. Our results suggest that CX3CL1-CX3CR1 interaction plays an important role in inflammatory cell migration into the muscle tissue of EAM mice. The results also point to the potential therapeutic usefulness of CX3CL1 inhibition and/or blockade of CX3CL1-CX3CR1 interaction in idiopathic inflammatory myopathy.
    Nov. 2005, Journal of immunology (Baltimore, Md. : 1950), 175(10) (10), 6987 - 96, English, International magazine
    Scientific journal

  • Migrating postmitotic neural precursor cells in the ventricular zone extend apical processes and form adherens junctions near the ventricle in the developing spinal cord.
    Yasuko Minaki, Eri Mizuhara, Koji Morimoto, Tomoya Nakatani, Yoshimasa Sakamoto, Yoko Inoue, Keiko Satoh, Toshio Imai, Yoshimi Takai, Yuichi Ono
    Postmitotic neural precursors are generated in the ventricular zone (VZ) of the developing neural tube and immediately migrate to the mantle layer (ML) where they differentiate into mature neurons. Although the regulation of neuronal differentiation and migration has extensively been studied, the behavior of the early postmitotic precursors migrating toward the ML is largely unknown. In this study, we have identified Neph3 as a specific marker for early postmitotic neural precursors in the VZ of the developing spinal cord. Analysis of Neph3 localization by immunofluorescence and immunoelectron microscopy revealed that early neural precursors in the VZ possessed not only pia-connected processes but also ones that reached the ventricle. This apical extension of processes was confirmed by analyzing another early postmitotic marker, Dll1 mRNA, which was actively transported toward the ventricle and accumulated at the termini of the processes. Furthermore, adherens junctions (AJs) were formed around the apical end of processes extending from Neph3- and Dll1 mRNA-positive postmitotic precursors. Taken together, these observations suggest that migrating early postmitotic neural precursors in the VZ of the developing spinal cord form a neuroepithelial cell-like bipolar morphology and communicate with their neighboring cells through AJs.
    Jul. 2005, Neuroscience research, 52(3) (3), 250 - 62, English, International magazine
    Scientific journal

  • [Fractalkine and inflammatory diseases].
    Toshio Imai, Miyuki Nishimura, Toshihiro Nanki, Hisanori Umehara
    The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.
    Jun. 2005, Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 28(3) (3), 131 - 9, Japanese, Domestic magazine
    Scientific journal

  • Identification of a novel cell-adhesive protein spatiotemporally expressed in the basement membrane of mouse developing hair follicle.
    Daiji Kiyozumi, Aki Osada, Nagisa Sugimoto, Charles N Weber, Yuichi Ono, Toshio Imai, Akiko Okada, Kiyotoshi Sekiguchi
    We used PCR-based cDNA subtraction to screen for genes up-regulated during mouse hair morphogenesis. One gene selected was predominantly expressed at the tip of developing hair follicles and encoded a protein characterized by the presence of twelve tandem repeats of approximately 120 amino acids and a novel N-terminal domain containing an Arg-Gly-Asp cell-adhesive motif. Immunohistochemistry demonstrated that the protein encoded by this gene, named QBRICK, was localized at the basement membrane zone of embryonic epidermis and hair follicles, in which it was more enriched at the tip rather than the stalk region. Cell adhesion assays showed that QBRICK was active in mediating cell-substratum adhesion through integrins containing alphav or alpha8 chain, but not integrin alpha5beta1. Immunohistochemistry showed that QBRICK colocalized with alphav-containing integrins in the interfollicular region, but with the alpha8-containing integrin at the tip region of developing hair follicles. These results, together, indicate that QBRICK is an adhesive ligand of basement membrane distinctively recognized by cells in the embryonic skin and hair follicles through different types of integrins directed to the Arg-Gly-Asp motif.
    May 2005, Experimental cell research, 306(1) (1), 9 - 23, English, International magazine
    Scientific journal

  • Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice.
    Atsushi Inoue, Hitoshi Hasegawa, Masashi Kohno, Mitsuko R Ito, Miho Terada, Toshio Imai, Osamu Yoshie, Masato Nose, Shigeru Fujita
    OBJECTIVE: Lupus nephritis is characterized by immune complex deposition and inflammatory cell infiltration into the renal glomeruli. Local generation of chemokines and the presence of chemokine receptors on the infiltrating cells may be involved in this process. Fractalkine (Fkn)/CX3CL1 and its receptor, CX3CR1, form one such chemokine system. We therefore undertook this study to investigate whether Fkn antagonist inhibits the initiation and progression of lupus nephritis in MRL/lpr mice. METHODS: NH(2)-terminally truncated Fkn/CX3CL1 analogs were transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, and injected subcutaneously into MRL/lpr mice. RESULTS: Fkn analogs truncated by >/=4 amino acid residues from the N-terminus failed to induce chemotaxis and calcium influx by CX3CR1-expressing cells. Of these, the most potent antagonist (Fkn-AT) lacked the 4 N-terminal amino acid residues. Fkn expression in the glomerulus was significantly increased in 12-week-old MRL/lpr mice. Expression was localized predominantly in the glomerular endothelial cells, but was occasionally observed in the mesangial cells and, to a lesser extent, in the interstitial microvasculature. Inoculation of MRL/lpr mice with Fkn-AT before the onset or during the early stages of lupus nephritis significantly reduced glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to a marked reduction in macrophage accumulation. In contrast, Fkn antagonist did not affect pneumonitis, sialadenitis, lymphadenopathy, or splenomegaly. CONCLUSION: We prepared a novel potent Fkn antagonist and demonstrated its ability to delay the initiation and ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach to lupus nephritis.
    May 2005, Arthritis and rheumatism, 52(5) (5), 1522 - 33, English, International magazine
    Scientific journal

  • T cell costimulation by fractalkine-expressing synoviocytes in rheumatoid arthritis.
    Hirokazu Sawai, Yong Wook Park, James Roberson, Toshio Imai, Jörg J Goronzy, Cornelia M Weyand
    OBJECTIVE: Patients with rheumatoid arthritis (RA) accumulate prematurely aged T cells that have acquired a new profile of regulatory receptors. Many of the de novo-expressed receptors are typically found on natural killer cells, including CX(3)CR1, the receptor for the chemokine fractalkine (FKN). This study explored whether interactions between CX(3)CR1 and FKN are relevant for T cell functions in rheumatoid synovitis. METHODS: FKN expression was examined by real-time polymerase chain reaction and immunohistochemistry. CX(3)CR1 expression on peripheral blood T cells was analyzed by flow cytometry. T cell activation was quantified by determining proliferative responses, interferon-gamma (IFNgamma) secretion, and granule release. Fibroblast-like synoviocyte (FLS)/T cell adhesion was measured by the retention of 5-carboxyfluorescein diacetate succinimidyl ester-labeled T cells on FLS monolayers. RESULTS: FKN was expressed on cultured synovial fibroblasts and hyperplastic synoviocytes in the rheumatoid tissue. Among CD4+ T cells, only senescent CD28- T cells were positive for CX(3)CR1 (P < 0.001). Such CD4+,CD28-,CX(3)CR1+ T cells strongly adhered to FLS, with soluble FKN blocking the interaction. FKN expressed on FLS costimulated T cell-activating signals and amplified proliferation, IFNgamma production, and expulsion of cytoplasmic granules. CONCLUSION: Senescent CD4+ T cells that accumulate in rheumatoid arthritis aberrantly express CX(3)CR1. FKN, which is membrane-anchored on synoviocytes, enhances CD4+ T cell adhesion, provides survival signals, and costimulates the production of proinflammatory cytokines as well as the release of granules. By virtue of their altered receptor profile, senescent CD4+ T cells receive strong stimulatory signals from nonprofessional antigen-presenting cells in the synovial microenvironment.
    May 2005, Arthritis and rheumatism, 52(5) (5), 1392 - 401, English, International magazine
    Scientific journal

  • Expression of MAEG, a novel basement membrane protein, in mouse hair follicle morphogenesis.
    Aki Osada, Daiji Kiyozumi, Ko Tsutsui, Yuichi Ono, Charles N Weber, Nagisa Sugimoto, Toshio Imai, Akiko Okada, Kiyotoshi Sekiguchi
    We screened for genes specifically expressed in the mesenchymes of developing hair follicles using representational differential analysis; one gene identified was MAEG, which encodes a protein consisting of five EGF-like repeats, a linker segment containing a cell-adhesive Arg-Gly-Asp (RGD) motif, and a MAM domain. Immunohistochemistry showed that MAEG protein was localized at the basement membrane of embryonic skin and developing hair follicles, while MAEG expression diminished at the tip of the hair bud. A recombinant MAEG fragment containing the RGD motif was active in mediating adhesion of keratinocytes to the substratum in an RGD-dependent manner. One of the adhesion receptors recognizing the RGD motif was found to be the alpha8beta1 integrin, the expression of which was detected in the placode close to MAEG-positive mesenchymal cells, but later became restricted to the tip of the developing hair bud. Given its localized expression at the basement membrane in developing hair follicles and the RGD-dependent cell-adhesive activity, MAEG may play a role as a mediator regulating epithelial-mesenchymal interaction through binding to RGD-binding integrins including alpha8beta1 during hair follicle development.
    Feb. 2005, Experimental cell research, 303(1) (1), 148 - 59, English, International magazine
    Scientific journal

  • Inhibition of fractalkine ameliorates murine collagen-induced arthritis.
    Toshihiro Nanki, Yasuyo Urasaki, Toshio Imai, Miyuki Nishimura, Kenzo Muramoto, Tetsuo Kubota, Nobuyuki Miyasaka
    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive infiltration of inflammatory cells in the synovium of multiple joints. We and others have shown that fractalkine (FKN/CX3CL1), a chemokine expressed on fibroblast-like synoviocytes and endothelial cells in RA synovium, may contribute to the accumulation of T cells, macrophages, and dendritic cells, which express CX3CR1, the receptor for FKN. This interaction might be involved in adhesion of the inflammatory cells to endothelial cells, migration into the synovium, and cytokine production. In this study, we examined the effect of FKN inhibition on murine collagen-induced arthritis. Anti-FKN mAb significantly lowered clinical arthritis score compared with control Ab, and reduced infiltration of inflammatory cells and bone erosion in the synovium. However, anti-FKN mAb did not affect the production of either serum anti-collagen type II (CII) IgG or IFN-gamma by CII-stimulated splenic T cells. Furthermore, treatment with anti-FKN mAb inhibited migration of adoptively transferred splenic macrophages into the inflamed synovium. Our results suggest that anti-FKN mAb ameliorates arthritis by inhibiting infiltration of inflammatory cells into the synovium. Thus, FKN can be a new target molecule for the treatment of RA.
    Dec. 2004, Journal of immunology (Baltimore, Md. : 1950), 173(11) (11), 7010 - 6, English, International magazine
    Scientific journal

  • Enhancement of serum- and platelet-derived growth factor-induced cell proliferation by Necl-5/Tage4/poliovirus receptor/CD155 through the Ras-Raf-MEK-ERK signaling.
    Shigeki Kakunaga, Wataru Ikeda, Tatsushi Shingai, Tsutomu Fujito, Akio Yamada, Yukiko Minami, Toshio Imai, Yoshimi Takai
    Necl-5/Tage4/poliovirus receptor/CD155 has been shown to be the poliovirus receptor and to be up-regulated in rodent and human carcinoma. We have found previously that mouse Necl-5 regulates cell motility. We show here that mouse Necl-5 is furthermore involved in the regulation of cell proliferation. Studies using a specific antibody against Necl-5 and a dominant negative mutant of Necl-5 revealed that Necl-5 enhanced the serum-induced proliferation of NIH3T3, Swiss3T3, and mouse embryonic fibroblast cells. Necl-5 enhanced the serum-induced activation of the Ras-Raf-MEK-ERK signaling, up-regulated cyclins D2 and E, and down-regulated p27(Kip1), eventually shortening the period of the G(0)/G(1) phase of the cell cycle in NIH3T3 cells. Necl-5 similarly enhanced the platelet-derived growth factor-induced activation of the Ras-Raf-MEK-ERK signaling and shortened the period of the G(0)/G(1) phase of the cell cycle in NIH3T3 cells. Necl-5 acted downstream of the platelet-derived growth factor receptor and upstream of Ras. Moreover, up-regulated Necl-5 was involved at least partly in the enhanced proliferation of transformed cells including NIH3T3 cells transformed by an oncogenic Ras or v-Src. These results indicate that Necl-5 plays roles not only in cell motility but also in cell proliferation.
    Aug. 2004, The Journal of biological chemistry, 279(35) (35), 36419 - 25, English, International magazine
    Scientific journal

  • Identification of novel keratinocyte-secreted peptides dermokine-alpha/-beta and a new stratified epithelium-secreted protein gene complex on human chromosome 19q13.1.
    Takeshi Matsui, Fumie Hayashi-Kisumi, Yoko Kinoshita, Sayaka Katahira, Kazumasa Morita, Yoshiki Miyachi, Yuichi Ono, Toshio Imai, Yoko Tanigawa, Tohru Komiya, Shoichiro Tsukita
    We performed high-throughput in situ hybridization screening of sections of mouse epidermis using an equalized skin cDNA library as probes and identified a novel gene giving rise to two splicing variants, both of which are expressed in the spinous layer. This gene was mapped between two genes encoding keratinocyte-related peptides, suprabasin and keratinocyte differentiation-associated protein (Kdap), on human chromosome 19q13.1. These gene products appeared to carry functional signal sequences. We then designated these two splicing variants as dermokine-alpha and -beta. Northern blotting and quantitative RT-PCR revealed that dermokine-alpha/-beta, suprabasin, and Kdap were highly expressed in stratified epithelia. In mouse embryonic development, dermokine-alpha/-beta began to be expressed during the period of stratification. Also, in differentiating primary cultured human keratinocytes, transcription of dermokine-alpha/-beta, suprabasin, and Kdap was induced. These findings indicated that dermokine-alpha/-beta, suprabasin, and Kdap are secreted from the spinous layer of the stratified epithelia and that these genes form a novel gene complex on the chromosome.
    Aug. 2004, Genomics, 84(2) (2), 384 - 97, English, International magazine
    [Refereed]
    Scientific journal

  • Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells.
    Takako Ooshio, Kenji Irie, Koji Morimoto, Atsunori Fukuhara, Toshio Imai, Yoshimi Takai
    Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules that are involved in formation of cadherin-based adherens junctions (AJs). The nectin-based cell-cell adhesion induces activation of Cdc42 and Rac small G proteins, which eventually enhances the formation of AJs through reorganization of the actin cytoskeleton. Although evidence has accumulated that nectins recruit cadherins to the nectin-based cell-cell adhesion sites through their cytoplasm-associated proteins, afadin and catenins, it is not fully understood how nectins are physically associated with cadherins. Here we identified a rat counterpart of the human LIM domain only 7 (LMO7) as an afadin- and alpha-actinin-binding protein. Rat LMO7 has two splice variants, LMO7a and LMO7b, consisting of 1,729 and 1,395 amino acids, respectively. LMO7 has calponin homology, PDZ, and LIM domains. Western blotting revealed that LMO7 was expressed ubiquitously in various rat tissues. Immunofluorescence and immunoelectron microscopy revealed that LMO7 localized at cell-cell AJs, where afadin localized, in epithelial cells of rat gallbladder. In addition, LMO7 localized at the cytoplasmic faces of apical membranes in the same epithelial cells. We furthermore revealed that LMO7 bound alpha-actinin, an actin filament-bundling protein, which bound to alpha-catenin. Immunoprecipitation analysis revealed that LMO7 was associated with both the nectin-afadin and E-cadherin-catenin systems. LMO7 was assembled at the cell-cell adhesion sites after both the nectin-afadin and E-cadherin-catenin systems had been assembled. These results indicate that LMO7 is an afadin- and alpha-actinin-binding protein that connects the nectin-afadin and E-cadherin-catenin systems through alpha-actinin.
    Jul. 2004, The Journal of biological chemistry, 279(30) (30), 31365 - 73, English, International magazine
    Scientific journal

  • Identification of genes expressed in the specific layer of mouse epidermis by the high-throughput in situ hybridization system
    Takeshi Matsui, Fumie Hayashi-Kisumi, Yoko Kinoshita, Sayaka Katahira, Kazumasa Morita, Yoshiki Miyachi, Yuichi Ono, Toshio Imai, Yoko Tanigawa, Tohru Komiya, Shoichiro Tsukita
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 75 - 75, English

  • Migrating postmitotic neural precursor cells in the ventricular zone apically extends the processes and form adherens junctions near the ventricle
    Yasuko Minaki, Koji Morimoto, Tomoya Nakatani, Yoshimasa Sakamoto, Yoko Inoue, Keiko Satoh, Eri Mizuhara, Toshio Imai, Yoshimi Takai, Yuichi Ono
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 84 - 84, English

  • Role of Nectin-like molecule-5/Poriovirus repeptor/CD155 on tumor metastasis into the lung
    Koji Morimoto, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Masakazu Takeuchi, Wataru Ikeda, Yoshimi Takai, Toshio Imai
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 42 - 42, English

  • Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells
    Takako Ooshio, Kenji Irie, Koji Morimoto, Atsunori Fukuhara, Toshio Imai, Yoshimi Takai
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 41 - 41, English

  • A novel counter ligand for coxseckie and adenovirus receptor (CAR), CARL, preferentially expressed on Th1 cells
    Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Koji Morimoto, Masakazu Takeuchi, Miyuki Nishimura, Toshio Imai
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 43 - 43, English

  • Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, Nectin-3-independent manner.
    Wataru Ikeda, Shigeki Kakunaga, Kyoji Takekuni, Tatsushi Shingai, Keiko Satoh, Koji Morimoto, Masakazu Takeuchi, Toshio Imai, Yoshimi Takai
    Cell migration plays roles in invasion of transformed cells and scattering of embryonic mesenchymal cells into surrounding tissues. We have found that Ig-like Necl-5/Tage4 is up-regulated in NIH3T3 cells transformed by an oncogenic Ras (V12Ras-NIH3T3 cells) and heterophilically trans-interacts with a Ca(2+)-independent Ig-like cell adhesion molecule nectin-3, eventually enhancing their intercellular motility. We show here that Necl-5 furthermore enhances cell migration in a nectin-3-independent manner. Studies using L fibroblasts expressing various mutants of Necl-5, NIH3T3 cells, and V12Ras-NIH3T3 cells have revealed that Necl-5 enhances serum- and platelet-derived growth factor-induced cell migration. The extracellular region of Necl-5 is necessary for directional cell migration, but not for random cell motility. The cytoplasmic region of Necl-5 is necessary for both directional and random cell movement. Necl-5 colocalizes with integrin alpha(V)beta(3) at leading edges of migrating cells. Analyses using an inhibitor or an activator of integrin alpha(V)beta(3) or a dominant negative mutant of Necl-5 have shown the functional association of Necl-5 with integrin alpha(V)beta(3) in cell motility. Cdc42 and Rac small G proteins are activated by the action of Necl-5 and required for the serum-induced, Necl-5-enhanced cell motility. These results indicate that Necl-5 regulates serum- and platelet-derived growth factor-induced cell migration in an integrin-dependent, nectin-3-independent manner, when cells do not contact other cells. We furthermore show here that enhanced motility and metastasis of V12Ras-NIH3T3 cells are at least partly the result of up-regulated Necl-5.
    Apr. 2004, The Journal of biological chemistry, 279(17) (17), 18015 - 25, English, International magazine
    Scientific journal

  • TNF-alpha and IL-4 regulate expression of fractalkine (CX3CL1) as a membrane-anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts.
    Mamoru Yoshikawa, Toshiharu Nakajima, Kenji Matsumoto, Naoko Okada, Toshiharu Tsukidate, Makoto Iida, Nobuyoshi Otori, Shin-Ichi Haruna, Hiroshi Moriyama, Toshio Imai, Hirohisa Saito
    The CX(3)C chemokine, fractalkine (FKN, CX(3)CL1), has multiple functions and exists as two distinct forms, a membrane-anchored protein and a soluble chemotactic peptide that cleaves from the cell surface FKN. In this study, we first demonstrated the expression of FKN in tumor necrosis factor (TNF)-alpha- and interleukin (IL)-4-stimulated human fibroblasts. The induction of FKN was observed for both forms. We also demonstrated monocyte chemotactic activity in the culture supernatant from the fibroblasts stimulated with these cytokines. These results suggest that TNF-alpha- and IL-4-stimulated fibroblasts may play an important role in accumulation of monocytes at inflammatory sites.
    Mar. 2004, FEBS letters, 561(1-3) (1-3), 105 - 10, English, International magazine
    Scientific journal

  • Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis.
    Noriko Ohtani, Haruo Ohtani, Takashi Nakayama, Hiroshi Naganuma, Eiichi Sato, Toshio Imai, Hiroshi Nagura, Osamu Yoshie
    Chronic gastritis is frequently associated with infection of Helicobacter pylori and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma cells. To address the mechanism of lymphocyte infiltration in chronic gastritis, we examined the expression of chemokines and their receptors using frozen sections of chronic gastritis, obtained from 23 patients who underwent gastrectomy for gastric cancer. By immunohistochemistry, lymphocytes in inflamed gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4 sparsely. The numbers of CCR5(+) cells, which were composed of mainly CD8(+) and partly CD4(+) T cells, were positively correlated with the degree of neutrophil infiltration, and decreased in areas with intestinal metaplasia or mucosal atrophy. RANTES/CCL5, one of the ligands of CCR5, was localized mainly in CD8(+) and partly CD4(+) T cells with a characteristic dotted pattern, and such lymphocytes were most densely distributed around the neck region of gastric glands. In situ hybridization confirmed the expression of CCL5 mRNA in these cells, and immunoelectron microscopy revealed localization of CCL5 in the membrane-bound granules, which most probably corresponded to the cytolytic granules of cytotoxic T cells. The numbers of CCL5(+) lymphocytes showed a close correlation with the degree of neutrophil infiltration and markedly decreased in intestinal metaplasia. In conclusion, our data suggest that, together with neutrophils, CCL5(+) T cells, presumably activated cytotoxic T cells, would play important roles in the active inflammatory process of chronic gastritis. Our data also suggest a self-recruiting mechanism involving CCR5 and CCL5 for tissue accumulation of such T cells.
    Mar. 2004, Laboratory investigation; a journal of technical methods and pathology, 84(3) (3), 368 - 75, English, International magazine
    Scientific journal

  • Fractalkine in vascular biology: from basic research to clinical disease.
    Hisanori Umehara, Eda T Bloom, Toshiro Okazaki, Yutaka Nagano, Osamu Yoshie, Toshio Imai
    Fractalkine (now also called CX3CL1) is a unique chemokine that functions not only as a chemoattractant but also as an adhesion molecule and is expressed on endothelial cells activated by proinflammatory cytokines, such as interferon-gamma and tumor necrosis factor-alpha. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes, which contain high levels of intracellular perforin and granzyme B, and on macrophages. Soluble fractalkine causes migration of NK cells, cytotoxic T lymphocytes, and macrophages, whereas the membrane-bound form captures and enhances the subsequent migration of these cells in response to secondary stimulation with other chemokines. Furthermore, stimulation through membrane-bound fractalkine activates NK cells, leading to increased cytotoxicity and interferon-gamma production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of various clinical disease states or processes, such as atherosclerosis, glomerulonephritis, cardiac allograft rejection, and rheumatoid arthritis. In addition, polymorphisms in CX3CR1, which reduce its binding activity to fractalkine, have been reported to increase the risk of HIV disease and to reduce the risk of coronary artery disease. This review will examine new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in various clinical conditions, especially in atherosclerosis and vascular injury.
    Jan. 2004, Arteriosclerosis, thrombosis, and vascular biology, 24(1) (1), 34 - 40, English, International magazine
    Scientific journal

  • Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells.
    Tatsushi Shingai, Wataru Ikeda, Shigeki Kakunaga, Koji Morimoto, Kyoji Takekuni, Shinsuke Itoh, Keiko Satoh, Masakazu Takeuchi, Toshio Imai, Morito Monden, Yoshimi Takai
    Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules that play roles in organization of a variety of cell-cell junctions in cooperation with or independently of cadherins. Four nectins have been identified. Five nectin-like molecules, which have domain structures similar to those of nectins, have been identified, and we characterized here nectin-like molecule-2 (Necl-2)/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1. Necl-2 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-1/TSLL1/SynCAM3 and nectin-3. Necl-2 was widely expressed in rat tissues examined. Necl-2 localized at the basolateral plasma membrane in epithelial cells of the mouse gall bladder, but not at specialized cell-cell junctions, such as tight junctions, adherens junctions, and desmosomes. Nectins bind afadin, whereas Necl-2 did not bind afadin but bound Pals2, a membrane-associated guanylate kinase family member known to bind Lin-7, implicated in the proper localization of the Let-23 protein in Caenorhabditis elegans, the homologue of mammalian epidermal growth factor receptor. These results indicate the unique localization of Necl-2 and its possible involvement in localization of a transmembrane protein(s) through Pals2.
    Sep. 2003, The Journal of biological chemistry, 278(37) (37), 35421 - 7, English, International magazine
    Scientific journal

  • Tage4/Nectin-like molecule-5 heterophilically trans-interacts with cell adhesion molecule Nectin-3 and enhances cell migration.
    Wataru Ikeda, Shigeki Kakunaga, Shinsuke Itoh, Tatsushi Shingai, Kyoji Takekuni, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Koji Morimoto, Masakazu Takeuchi, Toshio Imai, Yoshimi Takai
    Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a nectin- and actin filament-binding protein that connects nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with nectin-3 and regulates cell migration. Tage4 is tentatively re-named here nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of nectins.
    Jul. 2003, The Journal of biological chemistry, 278(30) (30), 28167 - 72, English, International magazine
    Scientific journal

  • Membrane-bound form of fractalkine induces IFN-gamma production by NK cells.
    Osamu Yoneda, Toshio Imai, Miyuki Nishimura, Michihiko Miyaji, Tsuneyo Mimori, Toshiro Okazaki, Naochika Domae, Hiroko Fujimoto, Yasuhiro Minami, Takeshi Kono, Eda T Bloom, Hisanori Umehara
    Natural killer (NK) cells participate in both innate and adaptive immunity, in part by their prompt secretion of cytokines including IFN-gamma, a pro-inflammatory cytokine with an important role in Th1 polarization. To assess the involvement of fractalkine in inflammatory processes, we examined the effect of fractalkine on IFN-gamma production by NK cells. Although soluble chemokines, including MCP-1 and RANTES as well as fractalkine, had a negligible effect on IFN-gamma production, immobilized fractalkine markedly induced IFN-gamma production by NK cells in a dose-dependent manner. Pretreatment of NK cells with the phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, completely inhibited the production of IFN-gamma induced by fractalkine, and pretreatment with the protein tyrosine kinase inhibitor, herbimycin A, partially suppressed the response, suggesting that augmentation of IFN-gamma production in response to fractalkine treatment of NK cells involves signaling through PI 3-K and protein tyrosine kinases. Furthermore, co-culture of NK cells with fractalkine-transfected 293E cells markedly enhanced IFN-gamma production by NK cells compared with co-culture with control 293E cells. These findings may indicate a paracrine feedback loop system in which endothelial cells may be activated to produce more fractalkine, and also suggest a role for fractalkine expressed on endothelial cells in Th1 polarization through the stimulation of IFN-gamma production by NK cells.
    Jan. 2003, European journal of immunology, 33(1) (1), 53 - 8, English, International magazine
    Scientific journal

  • Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis.
    Toshihiro Nanki, Toshio Imai, Kenji Nagasaka, Yasuyo Urasaki, Yoshinori Nonomura, Ken Taniguchi, Kenji Hayashida, Jun Hasegawa, Osamu Yoshie, Nobuyuki Miyasaka
    OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium. METHODS: Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry. RESULTS: CX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients. The peripheral CD4+ and CD8+ T cells expressing CX3CR1 predominantly produced interferon-gamma and tumor necrosis factor alpha, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1+,CD3+ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium. CONCLUSION: Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1+ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.
    Nov. 2002, Arthritis and rheumatism, 46(11) (11), 2878 - 83, English, International magazine
    Scientific journal

  • Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression.
    Miyuki Nishimura, Hisanori Umehara, Takashi Nakayama, Osamu Yoneda, Kunio Hieshima, Mayumi Kakizaki, Naochika Dohmae, Osamu Yoshie, Toshio Imai
    Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell adhesion and cell migration. Here we show that CX3CR1 defines peripheral blood cytotoxic effector lymphocytes commonly armed with intracellular perforin and granzyme B, which include NK cells, gammadelta T cells, and terminally differentiated CD8(+) T cells. In addition, soluble fractalkine preferentially induced migration of cytotoxic effector lymphocytes. Furthermore, interaction of cytotoxic effector lymphocytes with membrane-bound fractalkine promoted subsequent migration to the secondary chemokines, such as macrophage inflammatory protein-1beta/CC ligand 4 or IL-8/CXC ligand 8. Thus, fractalkine expressed on inflamed endothelium may function as a vascular regulator for cytotoxic effector lymphocytes, regardless of their lineage and mode of target cell recognition, through its ability to capture them from blood flow and to promote their emigration in response to other chemokines.
    Jun. 2002, Journal of immunology (Baltimore, Md. : 1950), 168(12) (12), 6173 - 80, English, International magazine
    Scientific journal

  • CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion.
    Alan M Fong, S Munir Alam, Toshio Imai, Bodduluri Haribabu, Dhavalkumar D Patel
    Fractalkine is a unique CX(3)C chemokine/mucin hybrid molecule that functions like selectins in inducing the capture of receptor-expressing cells. Because of the importance of tyrosine sulfation for ligand binding of the selectin ligand PSGL1, we tested the role of tyrosine sulfation for CX(3)CR1 function in cell adhesion. Tyrosine residues 14 and 22 in the N terminus of CX(3)CR1 were mutated to phenylalanine and stably expressed on K562 cells. Cells expressing CX(3)CR1-Y14F were competent in signal transduction but defective in capture by and firm adhesion to immobilized fractalkine under physiologic flow conditions. In static binding assays, CX(3)CR1-Y14F mutants had a 2-4-fold decreased affinity to fractalkine compared with wild type CX(3)CR1. By surface plasmon resonance measurements of fractalkine binding to biosensor chip-immobilized cell membranes, CX(3)CR1-Y14F mutants had a 100-fold decreased affinity to fractalkine. CX(3)CR1-expressing cell membranes treated with arylsulfatase to desulfate tyrosine residues also showed a 100-fold decreased affinity for fractalkine. Finally, synthesized, sulfated N-terminal CX(3)CR1 peptides immobilized on biosensor chips showed a higher affinity for fractalkine than non-sulfated peptides. Thus, we conclude that sulfation of tyrosine 14 enhances the function of CX(3)CR1 in cell capture and firm adhesion. Further, tyrosine sulfation may represent a general mechanism utilized by molecules that function in the rapid capture of circulating leukocytes.
    May 2002, The Journal of biological chemistry, 277(22) (22), 19418 - 23, English, International magazine
    Scientific journal

  • JEAP, a novel component of tight junctions in exocrine cells.
    Miyuki Nishimura, Mayumi Kakizaki, Yuichi Ono, Koji Morimoto, Masakazu Takeuchi, Yoko Inoue, Toshio Imai, Yoshimi Takai
    Tight junctions (TJs) consist of transmembrane proteins and many peripheral membrane proteins. To further characterize the molecular organization of TJs, we attempted here to screen for novel TJ proteins by the fluorescence localization-based expression cloning method. We identified a novel peripheral membrane protein at TJs and named it junction-enriched and -associated protein (JEAP). JEAP consists of 882 amino acids with a calculated molecular weight of 98,444. JEAP contained a polyglutamic acid repeat at the N-terminal region, a coiled-coil domain at the middle region, and a consensus motif for binding to PDZ domains at the C-terminal region. Exogenously expressed JEAP co-localized with ZO-1 and occludin at TJs in polarized Madin-Darby canine kidney cells, but not with claudin-1, JAM, or ZO-1 in L cells. Endogenous JEAP localized at TJs of exocrine cells including pancreas, submandibular gland, lacrimal gland, parotid gland, and sublingual gland, but not at TJs of epithelial cells of small intestine or endothelial cells of blood vessels. The present results indicate that JEAP is a novel component of TJs, which is specifically expressed in exocrine cells.
    Feb. 2002, The Journal of biological chemistry, 277(7) (7), 5583 - 7, English, International magazine
    Scientific journal

  • Hisanori Umehara, Seiji Goda, Toshio Imai, Yutaka Nagano, Yasuhiro Minami, Yoshiya Tanaka, Toshiro Okazaki, Eda T Bloom, Naochika Domae
    Wiley, Jun. 2001, Immunology & Cell Biology, 79(3) (3), 298 - 302, English
    [Refereed]
    Scientific journal

  • Osamu Yoshie, Toshio Imai, Hisayuki Nomiyama
    2001, Advances in immunology, 78, 57 - 110, English
    In book

  • GODA S
    Apr. 2000, Journal of Immunology, 164(8) (8), 4313 - 4320

  • Ishikawa-Mochizuki, I, M Kitaura, M Baba, T Nakayama, D Izawa, T Imai, H Yamada, K Hieshima, R Suzuki, H Nomiyama, O Yoshie
    Nov. 1999, FEBS LETTERS, 460(3) (3), 544 - 548, English
    [Refereed]
    Scientific journal

  • T Yoshida, D Izawa, T Nakayama, K Nakahara, M Kakizaki, T Imai, R Suzuki, M Miyasaka, O Yoshie
    Sep. 1999, FEBS LETTERS, 458(1) (1), 37 - 40, English
    [Refereed]
    Scientific journal

  • Christian Vestergaard, Hiroyuki Yoneyama, Masako Murai, Kohichiro Nakamura, Kunihiko Tamaki, Yuya Terashima, Toshio Imai, Osamu Yoshie, Tatsuro Irimura, Hitoshi Mizutani, Kouji Matsushima
    The american society for clinical investigation, 1999, Journal of clinical investigation, 104(8) (8), 1097 - 1105, English
    Scientific journal

  • Hiroyuki Yoneyama, Akihisa Harada, Toshio Imai, Masataka Baba, Osamu Yoshie, Yi Zhang, Hidemitsu Higashi, Masako Murai, Hitoshi Asakura, Kouji Matsushima
    The american society for clinical investigation, Dec. 1998, Journal of clinical investigation, 102(11) (11), 1933 - 1941, English
    Scientific journal

  • Novel lymphocyte-specific CC chemokines and their receptors
    O Yoshie, T Imai, H Nomiyama
    Nov. 1997, JOURNAL OF LEUKOCYTE BIOLOGY, 62(5) (5), 634 - 644, English
    Scientific journal

  • Morio Nagira, Toshio Imai, Kunio Hieshima, Jun Kusuda, Maaret Ridanpää, Shin Takagi, Miyuki Nishimura, Mayumi Kakizaki, Hisayuki Nomiyama, Osamu Yoshie
    Aug. 1997, Journal of biological chemistry, 272(31) (31), 19518 - 19524, English
    Scientific journal

  • M Baba, T Imai, M Nishimura, M Kakizaki, S Takagi, K Hieshima, H Nomiyama, O Yoshie
    Jun. 1997, JOURNAL OF BIOLOGICAL CHEMISTRY, 272(23) (23), 14893 - 14898, English
    Scientific journal

  • Ryu Yoshida, Toshio Imai, Kunio Hieshima, Jun Kusuda, Masataka Baba, Motoji Kitaura, Miyuki Nishimura, Mayumi Kakizaki, Hisayuki Nomiyama, Osamu Yoshie
    May 1997, Journal of biological chemistry, 272(21) (21), 13803 - 13809, English
    Scientific journal

  • Hisayuki Nomiyama, Toshio Imai, Jun Kusuda, Retsu Miura, David F. Callen, Osamu Yoshie
    Academic press inc., Feb. 1997, Genomics, 40(1) (1), 211 - 213, English
    Scientific journal

■ MISC
  • リウマチ性疾患の基礎研究 CX3CL1阻害による関節リウマチ関連間質性肺疾患の治療効果の検討
    水谷 聡, 西尾 純子, 山田 善登, 増岡 正太郎, 山田 壯一, 村岡 成, 石井 直人, 久保井 良和, 今井 俊夫, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2021, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65回, 307 - 307, Japanese

  • リウマチ性疾患の基礎研究 CX3CL1阻害による関節リウマチ関連間質性肺疾患の治療効果の検討
    水谷 聡, 西尾 純子, 山田 善登, 増岡 正太郎, 山田 壯一, 村岡 成, 石井 直人, 久保井 良和, 今井 俊夫, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2021, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65回, 307 - 307, Japanese

  • 抗フラクタルカイン抗体は強皮症様GVHDモデルマウスにおける皮膚硬化、間質性肺炎を抑制する
    宇都宮 慧, Vu Huy Luong, 知野 剛直, 尾山 徳孝, 松下 貴史, 小原 隆, 石井 直人, 久保井 良和, 待永 明仁, 小笠原 秀晃, 池田 わたる, 河野 鉄, 今井 俊夫, 長谷川 稔
    (一社)日本臨床免疫学会, Oct. 2020, 日本臨床免疫学会総会プログラム・抄録集, 48回, 78 - 78, Japanese

  • JAK阻害剤と開発中の薬剤 メトトレキサートによる治療で効果不十分な関節リウマチ患者を対象としたE6011(抗フラクタルカインモノクローナル抗体)の有効性・安全性の評価 臨床第2相二重盲検プラセボ対照試験
    田中 良哉, 竹内 勤, 山中 寿, 南木 敏宏, 梅原 久範, 安田 信之, 田胡 文利, 川久保 真, 北原 靖実, 河野 鉄, 今井 俊夫
    (一社)日本リウマチ学会, Aug. 2020, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64回, 371 - 371, Japanese

  • ヒト化抗フラクタルカイン抗体E6011を投与された関節リウマチ患者末梢血中のイムノフェノタイピング解析
    山田 知広, 西岡 恵理, 安田 信之, 河野 鉄, 今井 俊夫
    (一社)日本リウマチ学会, Aug. 2020, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64回, 640 - 640, Japanese

  • ヒト末梢血CX3CR1発現細胞を測定するためのフローサイトメトリー法の確立
    西岡 恵理[(房岡], 山田 知広, 安田 信之, 河野 鉄, 今井 俊夫
    (一社)日本リウマチ学会, Aug. 2020, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64回, 641 - 641, Japanese

  • 久保井 良和, 西村 美由希, 池田 わたる, 中谷 智哉, 関 幸恵, 山浦 唯, 小川 嘉奈, 村本 賢三, 水野 恵子, 小笠原 秀晃, 安田 信之, 今井 俊夫
    (一財)日本消化器病学会, Nov. 2019, 日本消化器病学会雑誌, 116(臨増大会) (臨増大会), A771 - A771, Japanese

  • 虚血再灌流障害関連拒絶反応におけるフラクタルカイン-CX3CR1シグナルに関する研究
    神澤 太一, 時田 大輔, 山川 貴史, 石郷岡 秀俊, 福田 洋典, 勝俣 陽貴, 宮入 聡, 石井 瑠美, 平井 敏仁, 雑賀 寛, 奥見 雅由, 今井 俊夫, 田邉 一成
    (一社)日本移植学会, Sep. 2019, 移植, 54(総会臨時) (総会臨時), 264 - 264, Japanese

  • 神澤 太一, 時田 大輔, 山川 貴史, 石郷岡 秀俊, 福田 洋典, 勝俣 陽貴, 宮入 聡, 石井 瑠美, 平井 敏仁, 雑賀 寛, 奥見 雅由, 今井 俊夫, 田邉 一成
    (一社)日本移植学会, Sep. 2019, 移植, 54(総会臨時) (総会臨時), 264 - 264, Japanese

  • 抗フラクタルカイン抗体を用いた関節リウマチ治療の可能性
    石井 直人, 久保井 良和, 今井 俊夫
    (株)北隆館, Aug. 2019, BIO Clinica, 34(8) (8), 871 - 876, Japanese

  • フラクタルカイン阻害による炎症免疫疾患治療の可能性 基礎研究から臨床開発へ
    今井 俊夫
    (一社)日本潰瘍学会, Jun. 2019, 潰瘍, 46, 72 - 72, Japanese

  • 今井 俊夫, 久保井 良和
    (一社)日本臨床リウマチ学会, Jun. 2019, 臨床リウマチ, 31(2) (2), 169 - 177, Japanese

  • 日本医療研究開発機構(AMED)が推進する糖尿病研究の展開 糖尿病網膜症の療のためのマクロファージを標的とした抗体薬の開発(Development of antibody drugs targeting macrophages for the treatment of diabetic retinopathy)
    植村 明嘉, 池田 わたる, 西山 功一, 今井 俊夫
    (一社)日本糖尿病学会, Apr. 2019, 糖尿病, 62(Suppl.1) (Suppl.1), S - 26, English

  • リウマチ性疾患の基礎研究-3 フラクタルカインによる間質性肺炎病態形成への関与
    山田 壯一, 楠 夏子, 佐藤 洋志, 村岡 成, 今井 俊夫, 川合 眞一, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2019, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63回, 518 - 518, Japanese

  • リウマチ性疾患の基礎研究-3 フラクタルカインによる間質性肺炎病態形成への関与
    山田 壯一, 楠 夏子, 佐藤 洋志, 村岡 成, 今井 俊夫, 川合 眞一, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2019, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63回, 518 - 518, Japanese

  • 抗フラクタルカイン抗体のマウス関節炎モデルにおける骨軟骨破壊抑制・滑膜炎抑制機序の解明
    根岸 香菜[星野], 中谷 智哉, 久保井 良和, 池田 わたる, 石井 直人, 安田 信之, 今井 俊夫
    (一社)日本リウマチ学会, Mar. 2019, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63回, 603 - 603, Japanese

  • 抗フラクタルカイン抗体のアトピー性皮膚炎マウスモデルにおける治療効果
    石井 直人, 中谷 智哉, 西岡 恵理, 小川 嘉奈, 今井 俊夫
    (公社)日本皮膚科学会, May 2018, 日本皮膚科学会雑誌, 128(5) (5), 1179 - 1179, Japanese

  • 日本人関節リウマチ患者におけるE6011(抗フラクタルカインモノクローナル抗体)の安全性・忍容性、薬物動態及び有効性の評価 臨床第1/2相First-in-Patient試験(52週間継続期データ)
    田中 良哉, 竹内 勤, 梅原 久範, 南木 敏宏, 安田 信之, 田胡 文利, 川久保 真, 北原 靖実, 河野 鉄, 今井 俊夫
    (一社)日本リウマチ学会, Mar. 2018, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62回, 725 - 725, Japanese

  • フラクタルカインによる間質性肺炎病態形成への関与
    山田 壯一, 楠 夏子, 佐藤 洋志, 村岡 成, 今井 俊夫, 川合 眞一, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2018, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62回, 780 - 780, Japanese

  • 抗フラクタルカイン(FKN)抗体のマクロファージ浸潤制御によるマウス肝炎モデルの病態改善
    西村 美由希, 久保井 良和, 村本 賢三, 水野 恵子, 小笠原 秀晃, 山内 敏彦, 安田 信之, 今井 俊夫
    (一財)日本消化器病学会, Sep. 2017, 日本消化器病学会雑誌, 114(臨増大会) (臨増大会), A732 - A732, Japanese

  • 抗フラクタルカイン(FKN)抗体の単球動態制御よるマウス大腸炎モデルの病態改善
    久保井 良和, 西村 美由希, 池田 わたる, 中谷 智哉, 小川 嘉奈, 村本 賢三, 水野 恵子, 小笠原 秀晃, 山内 敏彦, 安田 信之, 今井 俊夫
    (一財)日本消化器病学会, Sep. 2017, 日本消化器病学会雑誌, 114(臨増大会) (臨増大会), A793 - A793, Japanese

  • 石井 直人, 根岸 香菜, 中谷 智哉, 大黒 理勝, 池田 わたる, 久保井 良和, 山内 敏彦, 安田 信之, 今井 俊夫
    (一社)日本臨床免疫学会, Aug. 2017, 日本臨床免疫学会会誌, 40(4) (4), 296 - 296, Japanese

  • リウマチ性関節破壊に対する新規治療戦略 フラクタルカインを標的としたリウマチ性関節破壊に対する新規治療戦略
    今井 俊夫
    (一社)日本骨代謝学会, Jul. 2017, 日本骨代謝学会学術集会プログラム抄録集, 35回, 101 - 101, Japanese

  • コラーゲン誘発関節炎マウスモデルにおける抗フラクタルカイン抗体の骨・軟骨破壊抑制効果
    石井 直人, 根岸 香菜, 中谷 智哉, 大黒 理勝, 池田 わたる, 久保井 良和, 山内 敏彦, 安田 信之, 今井 俊夫
    (一社)日本骨代謝学会, Jul. 2017, 日本骨代謝学会学術集会プログラム抄録集, 35回, 176 - 176, Japanese

  • 安田 信之, 今井 俊夫, 河野 鉄
    (株)アークメディア, Jun. 2017, 肝胆膵, 74(6) (6), 933 - 939, Japanese

  • 関節リウマチの治療 生物学的製剤 日本人関節リウマチ患者におけるE6011(抗フラクタルカインモノクローナル抗体)の安全性・忍容性、薬物動態及び有効性の評価 臨床第1/2相First-in-Patient試験
    田中 良哉, 竹内 勤, 梅原 久範, 南木 敏宏, 赤真 秀人, 安田 信之, 田胡 文利, 川久保 真, 北原 靖実, 河野 鉄, 今井 俊夫
    (一社)日本リウマチ学会, Mar. 2017, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61回, 451 - 451, Japanese

  • 関節リウマチの病因・病態 関節リウマチの病態形成におけるレジスチンの作用の解明
    佐藤 洋志, 村岡 成, 楠 夏子, 増岡 正太郎, 山田 壯一, 進藤 恵実子, 川添 麻衣, 鹿野 孝太郎, 鏑木 誠, 田中 菜穂子, 金子 開知, 山本 竜大, 今井 俊夫, 川合 眞一, 南木 敏宏
    (一社)日本リウマチ学会, Mar. 2017, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61回, 507 - 507, Japanese

  • 自己免疫性肝疾患における基礎と臨床 新たな臨床試験の可能性まで 本邦より発信する抗ケモカイン抗体医薬、E6011
    河野 鉄, 安田 信之, 今井 俊夫
    (一社)日本肝臓学会, Oct. 2016, 肝臓, 57(Suppl.3) (Suppl.3), A665 - A665, Japanese

  • 肝細胞増殖因子(HGF)はアセトアミノフェン肝障害に対しても有用である
    元井 崇太郎, 井戸 章雄, 坪内 博仁, 豊田 裕子, 小原 隆, 太田 恵津子, 有田 貴久, 星野 香菜, 守屋 克裕, 副島 太啓, 今井 俊夫, 河野 鉄
    (一社)日本肝臓学会, Sep. 2016, 肝臓, 57(Suppl.2) (Suppl.2), A608 - A608, Japanese

  • フラクタルカインを標的とした炎症性腸疾患治療薬の可能性
    安田 信之, 久保井 良和, 今井 俊夫
    (株)北隆館, Dec. 2015, BIO Clinica, 30(14) (14), 1390 - 1395, Japanese

  • 間葉細胞の増殖を制御する新規核内因子Phf14の同定と機能解析
    北川 道憲, 武部 敦志, 尾野 雄一, 今井 俊夫, 中尾 和貴, 西川 伸一, 江良 択実
    (公社)日本生化学会, Dec. 2012, 日本生化学会大会プログラム・講演要旨集, 85回, 3P - 691, Japanese

  • ΔNp63は肺癌の組織形の決定因子の一つである(DeltaNp63 is one of the determinant factors in the histology of Lung Cancer)
    赤城 剛, 伊藤 智雄, 伊藤 真知子, 今井 俊夫, 笹井 研
    (一社)日本癌学会, Aug. 2012, 日本癌学会総会記事, 71回, 285 - 286, English

  • 【サイトカインのすべて(完全改訂版)】サイトカインの種類 ケモカイン CX3CL1/フラクタルカイン
    今井 俊夫
    (有)科学評論社, May 2012, 臨床免疫・アレルギー科, 57(Suppl.21) (Suppl.21), 483 - 490, Japanese

  • 溶解型ポリマーのミクロ構造化によるインテリジェント神経細胞足場を用いた中枢神経移植治療
    高島 健太, 西岡 恵理, 星野 真人, 川邊 裕祐, 上杉 健太朗, 八木 直人, 今井 俊夫, 中平 敦, 大隅 典子, 上月 正博, 小野寺 宏
    日本バイオマテリアル学会, Nov. 2011, 日本バイオマテリアル学会大会予稿集, 33回, 437 - 437, Japanese

  • がんと浸潤・転移 がん細胞と免疫細胞の浸潤機構(Cancer and its invasion, metastasis Adhesion molecules that regulate the cell trafficking of immune cells and cancer cells)
    今井 俊夫
    (一社)日本癌学会, Aug. 2010, 日本癌学会総会記事, 69回, 369 - 369, English

  • 血清中Dermokineを用いた早期胃癌大腸癌診断法と臨床病理学的解析(Serum Dermokine is useful for diagnosis of early gastric and colorectal cancer)
    菊池 正二郎, 松井 毅, 星 佐知, 熊野 達也, 渡邊 健次, 落合 登志哉, 今井 俊夫, 大辻 英吾
    (一社)日本癌学会, Aug. 2009, 日本癌学会総会記事, 68回, 244 - 244, English

  • サイトカイン・ケモカイン 多発性筋炎/皮膚筋炎におけるCX3CL1(fractalkine)発現の解析
    鈴木 文仁, 南木 敏宏, 廣畑 俊成, 今井 俊夫, 宮坂 信之
    (一社)日本リウマチ学会, Mar. 2009, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 53回・18回, 215 - 215, Japanese

  • 白血球動態の制御機構 AMICAとCARの相互作用はLFA-1の活性化を介してリンパ球の浸潤を亢進する(AMIGA, an adhesion molecule interacting with CAR, enhances lymphocyte transmigration by activating LFA-1)
    西岡 恵理[房岡], 山田 知広, 力津 絵津子, 西村 美由希, 片桐 晃子, 木梨 達雄, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2008, 日本免疫学会総会・学術集会記録, 38, 34 - 34, English

  • 新規分泌型サイトカインDermokineを用いた新しい早期大腸癌血清診断法の開発と臨床応用(Dermokine is noble tumor marker for diagnosis of early colorectal cancer)
    菊池 正二郎, 田儀 知之, 松井 毅, 今井 俊夫, 星 佐知, 喜住 文枝, 片山 政彦, 中西 正芳, 岡本 和真, 阪倉 長平, 落合 登志哉, 國場 幸均, 大辻 英吾
    (一社)日本癌学会, Sep. 2008, 日本癌学会総会記事, 67回, 259 - 259, English

  • 新規分泌型サイトカインDermokineの腺癌における発現解析(Immunohistochemical analysis of Dermokine in human adenocarcinoma)
    田儀 知之, 菊池 正二郎, 松井 毅, 喜住 文枝, 井田 曜子, 今井 俊夫, 星 佐知, 片山 政彦, 中西 芳正, 岡本 和真, 落合 登志哉, 國場 幸均, 大辻 英吾
    (一社)日本癌学会, Sep. 2008, 日本癌学会総会記事, 67回, 333 - 333, English

  • 北川 昌洋, 今井 俊夫, 菊池 正二郎, 窪田 健, 岡本 和真, 阪倉 長平, 落合 登志哉, 國場 幸均, 園山 輝久, 大辻 英吾
    (一社)日本消化器外科学会, Jul. 2008, 日本消化器外科学会雑誌, 41(7) (7), 1205 - 1205, Japanese

  • AMICA-CAR相互作用は移動性の輪状構造の形成によりTh1細胞の移動を刺激する(AMICA-CAR interaction stimulates the transmigration of Th1 cells by forming a migratory ring-like structure)
    房岡 恵理, 力津 絵津子, 山口 啓子, 井上 陽子, 西村 美由希, 今井 俊夫
    日本発生生物学会・日本細胞生物学会, May 2007, 日本発生生物学会・日本細胞生物学会合同大会要旨集, 40回・59回, 129 - 129, English

  • 今井 俊夫
    (有)科学評論社, Apr. 2006, 臨床免疫, 45(4) (4), 411 - 417, Japanese

  • 今井 俊夫
    (株)羊土社, Dec. 2005, 実験医学, 23(20) (20), 3072 - 3077, Japanese

  • 山口 啓子, 今井 俊夫
    (株)中山書店, Nov. 2005, Molecular Medicine, 42(12) (12), 1375 - 1381, Japanese

  • 抗フラクタルカイン/CX3CL1抗体のマウス炎症性腸疾患(IBD)モデルにおける治療効果
    久保井 良和, 西村 美由希, 水野 恵子, 今井 俊夫, 村本 賢三
    (NPO)日本免疫学会, Nov. 2005, 日本免疫学会総会・学術集会記録, 35, 32 - 32, Japanese

  • Necl-5/CD155とDNAM-1/CD226の結合によるがん細胞と血小板の細胞接着および肺転移への関与
    盛本 浩二, 山口 啓子, 濱口 晶子, 井上 陽子, 岡田 雅之, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2005, 日本免疫学会総会・学術集会記録, 35, 125 - 125, Japanese

  • 樹状細胞で発現する新規活性化受容体TARMの同定と機能解析
    水野 恵子, 小笠原 秀晃, 井上 陽子, 西村 美由希, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2005, 日本免疫学会総会・学術集会記録, 35, 156 - 156, Japanese

  • ConA肝炎におけるCX3CR1陽性マクロファージの役割
    西村 美由希, 久保井 良和, 水野 恵子, 盛本 浩二, 村本 賢三, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2005, 日本免疫学会総会・学術集会記録, 35, 162 - 162, Japanese

  • Th1細胞の選択的浸潤に関わる新規細胞接着分子
    山口 啓子, 井上 陽子, 力津 絵津子, 濱口 晶子, 盛本 浩二, 西村 美由希, 河野 鉄, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2005, 日本免疫学会総会・学術集会記録, 35, 166 - 166, Japanese

  • 久保井 良和, 村本 賢三, 今井 俊夫
    (株)最新医学社, Oct. 2005, 最新医学, 60(10) (10), 2350 - 2354, Japanese

  • Inhibition of fractalkine (CX3CL1) improves experimental autoimmune myositis in SJL/J mice.
    F Suzuki, T Nanki, T Imai, H Kikuchi, S Hirohata, H Kohsaka, N Miyasaka
    Sep. 2005, ARTHRITIS AND RHEUMATISM, 52(9) (9), S470 - S470, English
    Summary international conference

  • 大腸がんの肺転移モデルにおけるNectin-like molecule-5/Tage4/PVR/CD155の役割と作用機構
    盛本 浩二, 岡田 雅之, 池田 わたる, 高井 義美, 今井 俊夫
    (一社)日本癌学会, Sep. 2005, 日本癌学会総会記事, 64回, 100 - 101, Japanese

  • 井手 路子, 黒川 真奈絵, 池田 律子, 吉川 英志, 今井 俊夫, 橋本 卓雄, 鈴木 登
    (一社)日本炎症・再生医学会, Jul. 2005, 炎症・再生, 25(4) (4), 352 - 352, Japanese

  • 今井 俊夫, 西村 美由希, 南木 敏宏, 梅原 久範
    (一社)日本臨床免疫学会, Jun. 2005, 日本臨床免疫学会会誌, 28(3) (3), 131 - 139, Japanese

  • 膠原病関連疾患の病態解明と新規治療法の開発 抗fractalkine(FKN)抗体による実験的多発性筋炎の抑制
    鈴木 文仁, 南木 敏宏, 今井 俊夫, 菊地 弘敏, 広畑 俊成, 上阪 等, 宮坂 信之
    (一社)日本リウマチ学会, Apr. 2005, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 49回・14回, 115 - 115, Japanese

  • 炎症性腸疾患におけるfractalkine/CX3CR1の役割
    小林 拓, 岩上 祐子, 久松 理一, 岡本 晋, 今井 俊夫, 日比 紀文
    (一財)日本消化器病学会, Mar. 2005, 日本消化器病学会雑誌, 102(臨増総会) (臨増総会), A244 - A244, Japanese

  • ConA肝炎におけるフラクタルカイン-CX3CR1系の役割
    今井 俊夫, 西村 美由希, 久保井 良和, 水野 恵子, 村本 賢三
    (NPO)日本免疫学会, Nov. 2004, 日本免疫学会総会・学術集会記録, 34, 35 - 35, Japanese

  • 細胞接着分子CARに対する新規リガンドの同定とそのTh1細胞での選択的発現
    佐藤 啓子, 西村 美由希, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2004, 日本免疫学会総会・学術集会記録, 34, 42 - 42, Japanese

  • α4β7-MAdCAM-1およびCX3CR1-fractalkineを標的とした腸管GVHDの回避とGVT誘導の可能性
    上羽 悟史, 村井 政子, 米山 博之, 北畠 正大, 本津 茂人, 今井 俊夫, 島岡 猛士, 米原 伸, 石川 昌, 松島 綱治
    (NPO)日本免疫学会, Nov. 2004, 日本免疫学会総会・学術集会記録, 34, 146 - 146, Japanese

  • ケモカイン フラクタルカインの生物学的意義
    今井 俊夫
    医歯薬出版(株), Oct. 2004, 医学のあゆみ, 別冊(サイトカイン-state of arts) (サイトカイン-state of arts), 190 - 193, Japanese

  • 梅原 久範, 今井 俊夫, 堂前 尚親
    (株)先端医学社, Oct. 2004, 炎症と免疫, 12(6) (6), 735 - 742, Japanese

  • ネクチン様分子(Necl)-5/Tage4/PVR/CD155 Ras-Raf-MEK-ERKシグナルを介した細胞増殖の制御
    藤戸 努, 池田 わたる, 角永 茂樹, 真貝 竜史, 山田 章夫, 南 有紀子, 今井 俊夫, 高井 義美
    (一社)日本癌学会, Sep. 2004, 日本癌学会総会記事, 63回, 70 - 70, Japanese

  • 今井 俊夫
    (一社)日本炎症・再生医学会, Jul. 2004, 炎症・再生, 24(4) (4), 404 - 404, Japanese

  • 南木 敏宏, 浦崎 康代, 今井 俊夫, 村本 賢三, 窪田 哲朗, 宮坂 信之
    (一社)日本炎症・再生医学会, Jul. 2004, 炎症・再生, 24(4) (4), 478 - 478, Japanese

  • 上羽 悟史, 村井 政子, 米山 博之, 北畠 正大, 本津 茂人, 今井 俊夫, 島岡 猛士, 米原 伸, 石川 昌, 松島 綱治
    (一社)日本炎症・再生医学会, Jul. 2004, 炎症・再生, 24(4) (4), 508 - 508, Japanese

  • マウス胚性幹(ES)細胞由来神経前駆細胞の大脳移植治療
    池田 律子, 千葉 俊明, 黒川 真奈絵, 岳野 光洋, 濱田 真理, 吉川 英志, 近藤 靖, 菅野 巌, 中村 和浩, Kershaw Jeff, 長田 乾, 今井 俊夫, 橋本 卓雄, 鈴木 登
    (一社)日本脳神経外傷学会, Mar. 2004, 日本神経外傷学会プログラム・抄録集, 27回, 60 - 60, Japanese

  • 腸管GVHDにおけるドナーT細胞浸潤機構の解析
    上羽 悟史, 村井 政子, 米山 博之, 北畠 正大, 本津 茂人, 今井 俊夫, 石川 昌, 松島 綱治
    (NPO)日本免疫学会, Nov. 2003, 日本免疫学会総会・学術集会記録, 33, 50 - 50, Japanese

  • 抗fractalkine(FKN:CX3CL1)抗体による関節炎抑制効果の検討
    南木 敏宏, 浦崎 康代, 今井 俊夫, 村本 賢三, 窪田 哲朗, 宮坂 信之
    (NPO)日本免疫学会, Nov. 2003, 日本免疫学会総会・学術集会記録, 33, 224 - 224, Japanese

  • 抗Fractalkine抗体によるconcanavalin A-induced hepatitis(ConA肝炎)抑制機構の解析
    西村 美由希, 久保井 良和, 水野 恵子, 村本 賢三, 今井 俊夫
    (NPO)日本免疫学会, Nov. 2003, 日本免疫学会総会・学術集会記録, 33, 227 - 227, Japanese

  • 【ケモカイン・ケモカインレセプターをめぐって】リンパ球と血管内皮細胞との相互作用におけるフラクタルカインの関与
    梅原 久範, 西村 美由希, 今井 俊夫
    (有)科学評論社, Oct. 2003, 臨床免疫, 40(4) (4), 371 - 378, Japanese

  • ネクチン様分子(Necl)-5/Tage (1)ネクチン-3とヘテロな結合によるがん細胞の運動促進作用
    竹國 恭司, 池田 わたる, 角永 茂樹, 盛本 浩二, 佐藤 啓子, 竹内 勝一, 今井 俊夫, 高井 義美
    (一社)日本癌学会, Aug. 2003, 日本癌学会総会記事, 62回, 97 - 97, Japanese

  • ネクチン様分子(Necl)-5/Tage4 (2)ネクチン非依存性でインテグリン依存性のがん細胞の運動促進作用
    角永 茂樹, 池田 わたる, 竹國 恭司, 盛本 浩二, 佐藤 啓子, 竹内 勝一, 今井 俊夫, 高井 義美
    (一社)日本癌学会, Aug. 2003, 日本癌学会総会記事, 62回, 97 - 97, Japanese

  • ネクチン様分子Necl-2/TSLC1/SynCAM1 細胞間接着装置以外の側-基底細胞膜部位への局在とPals2の結合
    真貝 竜史, 池田 わたる, 角永 茂樹, 竹國 恭司, 盛本 浩二, 佐藤 啓子, 竹内 勝一, 今井 俊夫, 高井 義美
    (一社)日本癌学会, Aug. 2003, 日本癌学会総会記事, 62回, 317 - 317, Japanese

  • 西村 美由希, 今井 俊夫
    (株)先端医学社, Jun. 2003, 炎症と免疫, 11(4) (4), 435 - 442, Japanese

  • 真貝 竜史, 池田 わたる, 今井 俊夫, 高井 義美
    (株)メディカルレビュー社, Apr. 2003, がん分子標的治療, 1(2) (2), 96 - 103, Japanese

  • 腎発生におけるNECL2/TSLC1の関与について
    岩谷 博次, 伊藤 孝仁, 倭 正也, 鈴木 明, 上田 尚彦, 今井 圓裕, 堀 正二, 今井 俊夫, 池田 わたる, 高井 義美
    (一社)日本腎臓学会, Apr. 2003, 日本腎臓学会誌, 45(3) (3), 309 - 309, Japanese

  • FractalkineによるNK細胞のIFN-γ産生とTh1反応
    梅原 久範, 今井 俊夫, 吉藤 元, 川端 大介, 井村 嘉孝, 藤田 義正, 田中 真生, 藤井 隆夫, 三森 経世
    (一社)日本リウマチ学会, Mar. 2003, リウマチ, 43(2) (2), 305 - 305, Japanese

  • 抗fractalkine(CX3CL1)抗体による関節炎抑制効果の検討
    浦崎 康代, 南木 敏宏, 今井 俊夫, 村本 賢三, 窪田 哲朗, 宮坂 信之
    (一社)日本リウマチ学会, Mar. 2003, リウマチ, 43(2) (2), 307 - 307, Japanese

  • 吉川 衛, 飯田 誠, 中島 敏治, 松本 健治, 相田 奈緒, 今井 俊夫, 森山 寛, 斎藤 博久
    (一社)日本アレルギー学会, Oct. 2002, アレルギー, 51(9-10) (9-10), 994 - 994, Japanese

  • Fractalkine刺激によるNK細胞のIFN-γ産生とその解析
    米田 修, 井上 博, 西村 美由希, 今井 俊夫, 南 康博, 堂前 尚親, 梅原 久範
    (NPO)日本免疫学会, Oct. 2002, 日本免疫学会総会・学術集会記録, 32, 161 - 161, Japanese

  • マウス急性GVHDモデルにおけるドナー由来CD8+ T細胞でのCX3CR1の発現
    西村 美由希, 濱口 晶子, 盛本 浩二, 水野 恵子, 今井 俊夫
    (NPO)日本免疫学会, Oct. 2002, 日本免疫学会総会・学術集会記録, 32, 163 - 163, Japanese

  • 皮膚ホーミング性ヘルパーメモリーT細胞サブセットの特異的マーカーcutaneous lymphocyte antigenの生化学的実体としてのシアリル6-スルホルイスx
    大森 勝之, 今井 俊夫, 義江 修, 松島 綱治, 井澤 峯子, 金森 審子, 神奈木 玲児
    (NPO)日本免疫学会, Oct. 2002, 日本免疫学会総会・学術集会記録, 32, 165 - 165, Japanese

  • リンパ球と血管内皮細胞との接着におけるfractalkineの意義
    梅原 久範, 米田 修, 西村 美由紀, 宮地 理彦, 井上 博, 合田 征司, 堂前 尚親, 三森 経世, 義江 修, 今井 俊夫
    (NPO)日本免疫学会, Oct. 2002, 日本免疫学会総会・学術集会記録, 32, 167 - 167, Japanese

  • 梅原 久範, 今井 俊夫, 三森 経世
    (一社)日本炎症・再生医学会, Jun. 2002, 炎症・再生, 22(4) (4), 344 - 344, Japanese

  • 南木 敏宏, 今井 俊夫, Lipsky Peter E., 宮坂 信之
    (一社)日本炎症・再生医学会, Jun. 2002, 炎症・再生, 22(4) (4), 344 - 344, Japanese

  • Role of fractalkine/CX3CL1 in trafficking of circulating cytotoxic effector lymphocytes that are defined by CX3CR1 expression.
    M Nishimura, H Umehara, T Nakayama, O Yoneda, K Hieshima, M Kakizaki, N Dohmae, O Yoshie, T Imai
    Mar. 2002, FASEB JOURNAL, 16(5) (5), A1212 - A1212, English
    Summary international conference

  • CX3CL1/CX3CR1相互作用による慢性関節リウマチ(RA)滑膜組織へのT細胞浸潤
    南木 敏宏, 今井 俊夫, 長坂 憲治, 野々村 美紀, 谷口 顕, 林田 賢治, 長谷川 潤, 宮坂 信之
    (一社)日本リウマチ学会, Mar. 2002, リウマチ, 42(2) (2), 326 - 326, Japanese

  • Fractalkineによる血管内皮細胞傷害
    梅原 久範, 今井 俊夫, 田中 真生, 藤井 隆夫, 三森 恒世
    (一社)日本リウマチ学会, Mar. 2002, リウマチ, 42(2) (2), 327 - 327, Japanese

  • Role of chemokine in leukocytic infiltration to the kidney. (Ministry of Health, Labour and Welfare S).
    今井俊夫
    2002, 白血球浸潤を標的とした進行性腎障害の進展抑制に関する研究 平成13年度総括・分担研究報告書

  • FractalkineによるNK細胞のIFN-γ産生能とその解析
    米田 修, 井上 博, 西村 美由希, 今井 俊夫, 南 康博, 堂前 尚親, 梅原 久範
    (NPO)日本免疫学会, Dec. 2001, 日本免疫学会総会・学術集会記録, 31, 310 - 310, Japanese

  • Fractalkineのconcanavalin A-induced hepatitis(ConA肝炎)における機能解析
    久保井 良和, 村本 賢三, 菱沼 宇春, 西村 美由希, 今井 俊夫
    (NPO)日本免疫学会, Dec. 2001, 日本免疫学会総会・学術集会記録, 31, 312 - 312, Japanese

  • Fractalkine/CX3CR1のマウスリンパ球における解析
    西村 美由希, 村本 賢三, 今井 俊夫
    (NPO)日本免疫学会, Dec. 2001, 日本免疫学会総会・学術集会記録, 31, 309 - 309, Japanese

  • Hisanori Umehara, Eda T. Bloom, Toshiro Okazaki, Naochika Domae, Toshio Imai
    Elsevier ltd, 01 Nov. 2001, Trends in immunology, 22(11) (11), 602 - 607, English
    Book review

  • 梅原 久範, 今井 俊夫, 西村 美由希, 井上 博, 宮地 理彦, 米田 修, 堂前 尚親, 三森 経世
    (一社)日本臨床免疫学会, Oct. 2001, 日本臨床免疫学会会誌, 24(5) (5), 243 - 243, Japanese

  • Fractalkineの動脈硬化病変形成への関与について
    中井 浩司, 長野 豊, 梅原 久範, 今井 俊夫, 佐野 秀人, 横出 正之, 大東 道治, 大久保 直, 堂前 尚親
    (一社)日本動脈硬化学会, May 2001, 動脈硬化, 29(Suppl.) (Suppl.), 273 - 273, Japanese

  • 今井 俊夫, 西村 美由希
    (公社)日本薬学会, Apr. 2001, ファルマシア, 37(4) (4), 302 - 306, Japanese

  • 梅原 久範, 今井 俊夫, 堂前 尚親
    (有)科学評論社, Mar. 2001, 臨床免疫, 35(3) (3), 353 - 359, Japanese

  • 【7回膜貫通型受容体研究の新展開 ポストゲノム時代の受容体研究のゆくえ】7回膜貫通型受容体分子研究 ケモカイン受容体
    今井 俊夫
    医歯薬出版(株), Mar. 2001, 医学のあゆみ, 別冊(7回膜貫通型受容体研究の新展開) (7回膜貫通型受容体研究の新展開), 90 - 95, Japanese

  • 今井 俊夫, 梅原 久範
    (株)メディカルレビュー社, Feb. 2001, 免疫Immunology Frontier, 11(1) (1), 30 - 35, Japanese

  • Hisanori Umehara, Toshio Imai
    Prous science, 2001, Drug news and perspectives, 14(8) (8), 460 - 464, English
    Book review

  • エフェクターキラーリンパ球に選択的に発現するFractalkineレセプター,CX3CR1の解析
    西村 美由希, 米田 修, 梅原 久範, 堂前 尚親, 今井 俊夫, 義江 修
    (NPO)日本免疫学会, Nov. 2000, 日本免疫学会総会・学術集会記録, 30, 192 - 192, Japanese

  • 単球と血管内皮細胞との接着における接着性ケモカイン,fractalkineの機能
    梅原 久範, 合田 征司, 米田 修, 井上 博, 今井 俊夫, 義江 修, 今井 久夫, 堂前 尚親
    (NPO)日本免疫学会, Nov. 2000, 日本免疫学会総会・学術集会記録, 30, 192 - 192, Japanese

  • FractalkineによるNK細胞の活性化とIFN-γ産生能
    米田 修, 合田 征司, 井上 博, 今井 俊夫, 義江 修, 今井 久夫, 梅原 久範, 堂前 尚親
    (NPO)日本免疫学会, Nov. 2000, 日本免疫学会総会・学術集会記録, 30, 323 - 323, Japanese

  • 健常人におけるTリンパ球のroutine homingに特異的にはたらくセレクチンリガンド,シアリル6-スルホLe x
    大森 勝之, 光岡 ちか子, 井澤 峯子, 金森 審子, 今井 俊夫, 義江 修, 長谷川 均, 松島 綱治, 神奈木 玲児
    (NPO)日本免疫学会, Nov. 2000, 日本免疫学会総会・学術集会記録, 30, 195 - 195, Japanese

  • 【ケモカインハンドブック】ケモカインレセプター CCR4
    今井 俊夫
    (株)学研メディカル秀潤社, Nov. 2000, 細胞工学, 別冊(ケモカインハンドブック) (ケモカインハンドブック), 185 - 188, Japanese

  • 【ケモカインハンドブック】fractalkine
    今井 俊夫
    (株)学研メディカル秀潤社, Nov. 2000, 細胞工学, 別冊(ケモカインハンドブック) (ケモカインハンドブック), 142 - 145, Japanese

  • 【ケモカインハンドブック】MDC
    今井 俊夫
    (株)学研メディカル秀潤社, Nov. 2000, 細胞工学, 別冊(ケモカインハンドブック) (ケモカインハンドブック), 117 - 120, Japanese

  • 【ケモカインハンドブック】TARC
    今井 俊夫
    (株)学研メディカル秀潤社, Nov. 2000, 細胞工学, 別冊(ケモカインハンドブック) (ケモカインハンドブック), 114 - 116, Japanese

  • 【ケモカインハンドブック】ケモカインレセプター CX3CR1
    今井 俊夫
    (株)学研メディカル秀潤社, Nov. 2000, 細胞工学, 別冊(ケモカインハンドブック) (ケモカインハンドブック), 215 - 219, Japanese

  • 今井 俊夫
    (一社)日本臨床免疫学会, Aug. 2000, 日本臨床免疫学会会誌, 23(4) (4), 328 - 328, Japanese

  • 井上 博, 梅原 久範, 合田 征司, 米田 修, 今井 俊夫, 堂前 尚親
    (一社)日本炎症・再生医学会, Jul. 2000, 炎症, 20(4) (4), 520 - 520, Japanese

  • 梅原 久範, 米田 修, 井上 博, 合田 征司, 今井 俊夫, 堂前 尚親
    (一社)日本炎症・再生医学会, Jul. 2000, 炎症, 20(4) (4), 361 - 361, Japanese

  • 米田 修, 梅原 久範, 井上 博, 合田 征司, 今井 俊夫, 堂前 尚親
    (一社)日本炎症・再生医学会, Jul. 2000, 炎症, 20(4) (4), 472 - 472, Japanese

  • 中谷 公彦, 藤井 博司, 寺田 美穂, 有田 典正, 今井 俊夫, 能勢 眞人
    (一社)日本炎症・再生医学会, Jul. 2000, 炎症, 20(4) (4), 497 - 497, Japanese

  • 合田 征司, 梅原 久範, 井上 博, 米田 修, 今井 俊夫, 堂前 尚親
    (一社)日本炎症・再生医学会, Jul. 2000, 炎症, 20(4) (4), 531 - 531, Japanese

  • O Yoneda, T Imai, S Goda, H Inoue, A Yamauchi, T Okazaki, H Imai, O Yoshie, ET Bloom, N Domae, H Umehara
    Apr. 2000, JOURNAL OF IMMUNOLOGY, 164(8) (8), 4055 - 4062, English

  • 今井 俊夫
    (株)学研メディカル秀潤社, Apr. 2000, 細胞工学, 19(5) (5), 717 - 722, Japanese

  • ループス腎炎モデルマウスMRL/lprにおけるフラクタルカインの関与
    中谷 公彦, 藤井 博司, 寺田 美穂, 有田 典正, 今井 俊夫, 椎木 英夫, 土肥 和紘, 能勢 眞人
    (一社)日本腎臓学会, Apr. 2000, 日本腎臓学会誌, 42(3) (3), 212 - 212, Japanese

  • ループス腎炎モデルマウスにおける糸球体血管内皮細胞の接着分子のmicrodissectionによる解析
    中谷 公彦, 藤井 博司, 寺田 美穂, 有田 典正, 今井 俊夫, 能勢 眞人
    (一社)日本病理学会, Mar. 2000, 日本病理学会会誌, 89(1) (1), 227 - 227, Japanese

  • CX3C-Chemokine,fractalkineによるNK細胞活性化と血管内皮細胞傷害との関係
    梅原 久範, 米田 修, 井上 博, 合田 征司, 今井 俊夫, 義江 修, 堂前 尚親
    (株)ミノファーゲン製薬, Jan. 2000, Minophagen Medical Review, 45(1) (1), 48 - 48, Japanese

  • サイトカイン・ケモカイン ケモカインと接着分子のハイブリッド分子fractalkine
    今井 俊夫
    (株)中外医学社, Dec. 1999, Annual Review免疫, 2000, 186 - 192, Japanese

  • 今井 俊夫
    (株)ニュー・サイエンス社, Nov. 1999, 細胞, 31(13) (13), 525 - 529, Japanese

  • THP-1細胞と細胞外マトリックス蛋白との接着におけるCX3C-ケモカイン,Fractalkineの影響
    合田 征司, 梅原 久範, 米田 修, 井上 博, 今井 俊夫, 義江 修, 今井 久夫, 堂前 尚親
    (NPO)日本免疫学会, Oct. 1999, 日本免疫学会総会・学術集会記録, 29, 283 - 283, Japanese

  • NK細胞の内皮細胞接着能及び細胞傷害活性に及ぼすCX3C-Chemokine,Fractalkineの影響
    米田 修, 梅原 久範, 井上 博, 合田 征司, 今井 俊夫, 義江 修, 今井 久夫, 堂前 尚親
    (NPO)日本免疫学会, Oct. 1999, 日本免疫学会総会・学術集会記録, 29, 290 - 290, Japanese

  • マウス喘息モデルに対するTARCの役割
    河崎 伸, 米山 博之, 滝沢 始, 今井 俊夫, 義江 修, 松島 綱治
    (NPO)日本免疫学会, Oct. 1999, 日本免疫学会総会・学術集会記録, 29, 85 - 85, Japanese

  • 今井 俊夫
    医歯薬出版(株), Aug. 1999, 医学のあゆみ, 190(9) (9), 817 - 817, Japanese

  • Selective recruitment of CCR4-bearing T^h2 cells toward antigen-presenting celsl by the CC chemokines thymus and activation-regulated chemokine and macropahe-derived chemokine
    IMAI Toshio, NAGIRA Morio, TAKAGI Shin, KAKIZAKI Mayumi, NISHIMURA Miyuki, WANG Jianbin, GRAY Patrick W., MATSUSHIMA Kouji, YOSHIE Osamu
    1999, Int. Immunol., 11(1) (1), 81 - 88, English

  • 【ケモカインとそのレセプター】新規ケモカイン・ケモカイン受容体と免疫システム
    今井 俊夫
    (株)ニュー・サイエンス社, Nov. 1998, 組織培養工学, 24(12) (12), 457 - 460, Japanese

  • THP-1細胞と細胞外マトリックス蛋白との接着におけるCX3C-ケモカイン,Fractalkineの影響
    合田 征司, 梅原 久範, 米田 修, 井上 博, 今井 俊夫, 義江 修, 今井 久夫, 堂前 尚親
    (一社)日本臨床免疫学会, Oct. 1998, 日本臨床免疫学会会誌, (26回抄録集) (26回抄録集), 200 - 200, Japanese

  • NK細胞の内皮細胞接着能及び細胞傷害活性に及ぼすCX3C-Chemokine,Fractalkineの影響
    米田 修, 梅原 久範, 井上 博, 合田 征司, 今井 俊夫, 義江 修, 堂前 尚親
    (一社)日本臨床免疫学会, Oct. 1998, 日本臨床免疫学会会誌, (26回抄録集) (26回抄録集), 207 - 207, Japanese

  • 急性肝障害発症マウスモデルにおけるケモカイン,TARCの役割
    米山 博之, 原田 明久, 今井 俊夫, 義江 修, Yi Zhang, 東 秀光, 村井 政子, 朝倉 均, 松島 綱治
    (一社)日本臨床免疫学会, Oct. 1998, 日本臨床免疫学会会誌, (26回抄録集) (26回抄録集), 152 - 152, Japanese

  • 今井 俊夫
    (株)学研メディカル秀潤社, Jul. 1998, 細胞工学, 17(7) (7), 1046 - 1053, Japanese

  • NK細胞の内皮細胞接着能および細胞傷害活性に及ぼすCX3C-Chemokine,Fractalkineの影響
    米田修, 梅原久範, 井上博, 合田征司, 今井俊夫, 義江修, 堂前尚親
    1998, 日本免疫学会総会・学術集会記録, 28

  • A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes
    K Hieshima, T Imai, M Baba, K Shoudai, K Ishizuka, T Nakagawa, J Tsuruta, M Takeya, Y Sakaki, K Takatsuki, R Miura, G Opdenakker, J VanDamme, O Yoshie, H Nomiyama
    Aug. 1997, JOURNAL OF IMMUNOLOGY, 159(3) (3), 1140 - 1149, English

  • Cloning of new human CC type chemokine ELC and identification of its receptor CCR7/EBI1.
    吉田立, 今井俊夫, 馬場正隆, 柳楽盛男, 義江修, 野見山尚之, 稗島州雄, 西村美由希, 柿崎真由美
    1997, 日本免疫学会総会・学術集会記録, 27

  • Cloning of new human CC type chemokine LARC and identification of its receptor CCR6.
    馬場正隆, 今井俊夫, 高木信, 義江修
    1997, 日本免疫学会総会・学術集会記録, 27

  • Identification and molecule functional analysis of a receptor CX3CR1 of membrane linkage type CX3C chemokine (fractalkine) to induce the random migration of leucocyte and the cell adhesion.
    今井俊夫, 馬場正隆, 柳楽盛男, 高木信, 義江修, 野見山尚之, 稗島州雄, 西村美由希, 柿崎真由美
    1997, 日本免疫学会総会・学術集会記録, 27

  • Characterization of Human CC Chemokine PARC.
    稗島州雄, 今井俊夫, 馬場正隆, 三浦れつ, 義江修, 野見山尚之
    1997, 日本分子生物学会年会プログラム・講演要旨集, 20th

  • Molecular Cloning of Human CC Chemokine PARC cDNA and Characterization of Its Gene.
    田崎容子, 稗島州雄, 今井俊夫, 馬場正隆, 飯尾雅嘉, 三浦れつ, 義江修, 野見山尚之
    1997, 日本分子生物学会年会プログラム・講演要旨集, 20th

  • Structure of new C type ”chemokine” SCM-1/Lymphotactin gene.
    高木信, 今井俊夫, 義江修
    1996, 日本免疫学会総会・学術集会記録, 26

  • Human new chemokine gene found from EST database.
    稗島州雄, 野見山尚之, 今井俊夫, 楠田潤, 程肇, 義江修, 榊佳之, 高月清, 三浦きよし
    1996, 日本分子生物学会年会プログラム・講演要旨集, 19th

  • C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63
    IMAI T
    1992, J Immunol, 149, 2879 - 2886

■ Research Themes
  • OKUMI Masayoshi, HIRAI toshihito, KANZAWA taichi, IMAI toshio, TOKITA daisuke
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Tokyo Women's Medical University, 01 Apr. 2016 - 31 Mar. 2019
    We transplanted allogeneic donor hearts preserved at 4℃ for 8 hours (IRI group) or 0.5 hours (control group). The survival rate of allografts in the IRI group was significantly lower than that in the control group. To clarify the importance of CX3CR1 in IRI-related rejection, donor hearts preserved at 4℃ for 8 hours were transplanted in CX3CR1 knock-out mice. The survival rate of allografts in these mice was significantly higher than that in the wild-type mice. Anti-fractalkine (FKN) antibody prolonged graft survival in mice transplanted with donor hearts preserved at 4℃ for 8 hours. In conclusion, FKN-CX3CR1 interaction is crucial in IRI-related rejection in allogeneic transplantation. Anti-FKN antibody has a potential to improve the outcome of deceased-donor transplantation by blocking FKN-CX3CR1 interaction.

  • The roles of fractalkine in pathogenesis of systemic sclerosis
    UMEHARA Hisanori, MIMORI Tsuneyo, OGAWA Noriyoshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), 2003 - 2005
    Leukocyte adhesion and trafficking at the endothelium requires both adhesion molecules and chemotactic factors. Fractalkine (CX3C) is a unique chemokine, and expressed on TNF-α- and IL-1-activated endothelial cells (ECs). Fractalkine receptor, CX3CR1, is expressed on NK cells, monocytes and some portion of CD4- and CD8-positive T cells. Interactions between fractalkine and CX3CR1 can mediate not only chemotaxis, but also cell adhesion in the absence of substrates for other adhesion molecules. Furthermore, fractalkine activates NK cells, leading to increased cytotoxicity and IFN-γ production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of rheumatoid arthritis and allied conditions. This review will examine new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in rheumatic diseases.

  • フラクタルカインおよびレセプター発現と癌の悪性度・転移との関連
    梅原 久範, 今井 俊夫, 岡崎 俊朗
    日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 京都大学, 2003 - 2004
    癌の悪住度は,転移の頻度および抗癌剤や腫瘍殺傷能を有する免疫担当細胞に対する感受性などにより規定される.フラクタルカインは細胞接着と遊走活性を合わせ持つケモカインで細胞の接着と遊走に深く関わっている.腫瘍細胞におけるフラクタルカイン発現は細胞傷害性T細胞に対する感受性を示し,癌の遊走と転移および免疫担当細胞に対する抵抗性など癌の悪性度に深く関わっている.我々は,1)フラクタルカインレセプター(CX3CR1)がNK細胞とCD8陽性T細胞に発現していること,2)フラクタルカインが接着分子と協調的に細胞接着を誘導すること,3)フラクタルカインが選択的にCD8陽性T細胞やNK細胞を遊走させること,5)フラクタルカインがNK細胞から傷害顆粒を放出させること,6)フラクタルカイン発現癌細胞がNK細胞に高い感受性を示すこと,7)固層化フラクタルカインがNK細胞を活性化しIFN-γ産生を増強することを明らかにした.このように,腫瘍細胞がフラクタルカインを発現している場合には,CD8陽性T細胞やNK細胞により傷害を受け除去され,逆にCX3CR1を発現している場合には,内皮細胞との接着増強,フラクタルカインによる遊走増強を受け,浸潤や転移が増強する可能性がある.

  • IMPROVEMENT OF ADOPTIVE IMMUNE THERAPY FOR CERVIAL CANCER
    UMEHARA Hisanori, IMAI Toshio, MIMORI Tsuneyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), KYOTO UNIVERSITY, 2001 - 2003
    For the improvement of adoptive immune therapy, we investigated the mechanisms of the major side effects, vascular leak syndrome and functional roles of membrane lipid rafts of NK cells. We found 1) After identification of the receptor for fractalkine, CX3CR1, we reported that CX3CR1 was expressed on CD 14+ monocytes, CD 16+ NK cells and CD8+ T cells. 2) Integrins and fractalkine synergistically enhanced cell adhesion. 3) Fractalkine enhanced cell adhesion and granular exocytosis of NK cells. Fractalkine expressed on activated endothelial cells caused NK cell lysis and vascular injury. 4) Fractalkine activated NK cells and produced IFN-gamma, which may mediate Th1-type immune response. 5) Membrane lipid rafts was involved in cytotoxicity of NK cells. 6) Sphingomyelin of the membrane was important for cellular activation and apoptosis. These results may provide the new insight for the improvement for adoptive immune therapy by reducing its side effects, vascular leak syndrome, and improved the efficacy of therapy.

  • 血管炎発症モデルにおけるCX3C-ケモカイン,Fractalkineの関与
    梅原 久範, 今井 俊夫, 三森 恒世, 堂前 尚親
    日本学術振興会, 科学研究費助成事業 萌芽研究, 萌芽研究, 京都大学, 2001 - 2002
    Fractalkineは活性化血管内皮細胞上に発現する膜型ケモカインである.我々はfractalkine receptor (CX3CR1)を世界に先駆けて同定し,CD14+単球,CD16+NK細胞,CD8+T細胞上に発現していること,およびfractalkineが従来のケモカインと異なり接着分子として作用することを報告した(Imai, Cell91:521-530,1997).咋年度に引き続き,LPS投与によるマウス血管炎モデルあるいはMRL/lprマウスにおける抗fractalkine抗体による血管炎予防効果の検討を行った.単球やNK細胞と血管内皮細胞との接着や内皮傷害の基礎的検討により,1)可溶型fractalkineは単球のfibonectinやICAM-1に対する接着をも増強した.2)fractalkine遺伝子導入したECV細胞株を用いた検討より,細胞膜上に発現したfractalkineが有意に単球やNK細胞の接着を増強した.3)fractalkineは濃度依存性にNK細胞の抗腫瘍細胞殺傷能を増強し,fractalkine発現ECV細胞やヒト胎児血管内皮細胞を著明に傷害した.4.マウス腹腔内にLPSを500μg投与すると,ほぼ前例がエンドトキシンショックと全身臓器の血管炎を発症し死亡するが,抗fractalkine抗体を24時間前およびLPSと同時に腹腔内投与すると,70%のマウスが生存した.これらの結果は,炎症に伴い産生されたサイトカインにより活性化した血管内皮細胞がfractalkineを発現し,単球やNK細胞の接着を誘導し血管炎を誘導していることを示している.抗fractalkine抗体は,この作用を抑制し,血管炎発症を阻止しうる可能性を強く示唆している.

  • 敗血症ショックに対する抗fractalkine抗体の予防効果
    梅原 久範, 堂前 尚親, 今井 俊夫, 三森 経世
    日本学術振興会, 科学研究費助成事業 特定領域研究(C), 特定領域研究(C), 京都大学, 2001 - 2001
    fractalkineは活性化血管内皮細胞上に発現する膜型ケモカインである.我々はfractalkine receptor(CX3CR1)を世界に先駆けて同定し,CD14+単球,CD16+NK細胞,CD8+T細胞上に発現していること,およびfractalkineが従来のケモカインと異なり接着分子として作用することを報告した(Imai, Cell 91:521-530,1997).今年度は,LPS投与によるマウス敗血症モデルにおける抗fractalkineによる予防効果を検討するために,単球やNK細胞と血管内皮細胞との接着や内皮傷害におけるfractalkineの関与を検討した.1)可溶型fractalkineは単球のfibonectinやICAM-1に対する接着をも増強した.2)ECV細胞株にfractalkine遺伝子を導入したtransfectantを作成し,単球やNK細胞との接着を検討したところ,細胞膜上に発現したfractalkineが有意に細胞接着を増強することを認めた.さらに,fractalkineのNK細胞活性化効果を検討したところ,3)fractalkineは濃度依存性にNK細胞の抗腫瘍細胞殺傷能を増強した.4)この作用増強は,NK細胞からの頼粒放出増強によることが明らかとなった.5)実際に,fractalkine発現ECV細胞やヒト胎児血管内皮細胞を標的細胞とした実験系により,NK細胞がfractalkine発現血管内皮細胞を著明に傷害することを見いだした.この結果は,敗血症時に産生されるサイトカインにより,活性化した血管内皮細胞がfractalkineを発現し,単球やNK細胞の接着を誘導し,自身が傷害されていることを強く示唆するものと考えられた.

  • Role of CX_3C-chemokine, fractalkine on pathogenesis of periodontitis
    UMEHARA Hisanori, DOMAE Naochika, IMAI Toshiiio, KONO Takeshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)., Grant-in-Aid for Scientific Research (B)., Osaka Dental University, 1999 - 2000
    Periodontitis is the chronic inflammation caused by oral bacteria, such as Porphyromonas gingivalis in dental plaque. Accumulation of immunocompetent cells, such as T cells, NK cells and macrophages in the inflammatory gingiva may be involved in the pathogenesis. The vascular endothelium plays an important role in the recruitment and migration of circulating effector cells into sites of inflammation and immune response. Fractalkine, a recently identified chemokine is expressed in a membrane-bound form on TNF-α-and IL-1-activated endothelial cells. We examined the molecular and biological functions of fractalkine on adhesion between effector cells and endothelial cells, and found the following evidences : 1.CX_3C-chemokine, fractalkine enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and independent mechanisms (Reference 1). THP-1 cells express mRNA encoding a receptor for fractalkine, CX_3CR1, determined by northern blotting and Scatchard analysis. Soluble-fractalkine enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose-dependent manner. 2.Fractalkine-mediated endothelial cell injury by NK cells (Reference 2). Freshly separated NK cells expressed the fractalkine receptor (CX_3CR1) determined by FACS analysis. Soluble fractalkine enhanced NK cell cytolytic activity against K562 target cells. Transfection of fractalkine cDNA into ECV304 cells or HUVECs resulted in increased adhesion of NK cells and susceptibility to NK cell-mediated cytolysis compared to control transfection. 3.CX_3C-chemokine, fractalkine functions predominantly as an adhesion molecule in monocytic cell line, THP-1 (Reference 3). Co-immobilized fractalkine with fibronectin or ICAM-1 enhanced adhesion of THP-1 cells, which express the fractalkine receptor (CX_3CR1), compared beyond that observed with each alone. However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to MCP-1 which induced a strong chemotactic response.

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