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KOTO ShusukeUniversity Hospital / NeurologyAssistant Professor
Research activity information
■ Award- Jul. 2023 一般財団法人 敬愛まちづくり財団,神戸大学, Maenosono Memorial Young Scientist Best Paper Award, Transcription Factor c-Maf Promotes Immunoregulation of Programmed Cell Death 1–Expressed CD8+ T Cells in Multiple Sclerosis
- Oct. 2022 The Japanese Society for Neuroimmunology, Young Neuroimmunologist Aword, 転写因子c-Mafは多発性硬化症におけるCD8+ T細胞のPD-1発現を促進し、免疫抑制機能を発揮する
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S236 - S236, Japanese多発性硬化症患者脳脊髄液のCD8+ T細胞上のPD-1発現上昇が良好な長期予後と相関する
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S437 - S437, Japanese労作時呼吸困難を呈した孤発性成人発症型ネマリンミオパチー疑いの一例
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S437 - S437, Japanese神経生理検査から脊髄神経根障害と局在診断したサルコイドーシスの1例
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S438 - S438, Japanese急激の運動障害の増悪を呈したアレキサンダー病II型の一例
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(10) (10), 761 - 761, Japanese呼吸停止に至ったが免疫治療により著明に改善した成人発症急性散在性脳脊髄炎(ADEM)の一例
- (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(10) (10), 761 - 761, Japanese子宮頸癌に対する放射線化学療法後に発症した重症筋無力症関連筋炎の一例
- (一社)日本てんかん学会, Sep. 2024, てんかん研究, 42(2) (2), 483 - 483, Japanese強制正常化をきたし治療に難渋した右前頭葉てんかんの1例
- (一社)日本神経学会, Aug. 2024, 臨床神経学, 64(8) (8), 604 - 604, Japanese認知機能低下を契機に診断に至りcARTが奏効したAIDSの一例
- BACKGROUND AND OBJECTIVES: Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. METHODS: Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19+ IgD-, CD27-) and plasmablasts (PBs; CD19+, CD27hi, CD38hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab. RESULTS: DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200+ PBs produced more IL-10 than CD200- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200+ PBs than patients during the acute attacks. DISCUSSION: Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200+ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.Jul. 2024, Neurology(R) neuroimmunology & neuroinflammation, 11(4) (4), e200266, English, International magazineScientific journal
- Apr. 2024, Immunological Medicine, EnglishScientific journal
- (一社)日本神経学会, Mar. 2024, 臨床神経学, 64(3) (3), 227 - 227, Japanese側脳室周囲に造影効果病変を伴った視神経脊髄炎スペクトラム障害(NMOSD)の一例
- (一社)日本神経学会, Mar. 2024, 臨床神経学, 64(3) (3), 230 - 230, Japanese同側顔面および上肢の感覚障害をきたした後脊髄動脈領域梗塞の一例
- Feb. 2024, Clinical and Experimental NeuroimmunologyScientific journal
- Japan Stroke Society, 2024, Japanese Journal of StrokeScientific journal
- BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. CD8+ T cells are prominently found at inflammatory sites. Recent advances in understanding checkpoint molecules, including programmed cell death 1 (PD-1), expressed on CD8+ T cells, highlight the immune regulatory roles of this T-cell subset; however, the role of CD8+ T cells in MS is unclear. Thus, we aimed to reveal the characteristics of PD-1-expressed (PD-1+) CD8+ T cells in MS. METHODS: We performed a cohort, case-control study for phenotyping analysis of PD-1+CD8+ T cells in disease remission and flare states using CSF and peripheral blood samples of 45 patients with MS or clinically isolated syndrome and 12 healthy subjects. We further analyzed the transcriptome of sorted PD-1+CD8+ T cells obtained from interferon (IFN)-β-treated patients and validated their regulatory machinery using in vitro cell culture assays with lentiviral gene transfer. RESULTS: In the disease remission state, PD-1+CD8+ T cells were decreased in the peripheral blood of patients with MS and resolved in patients treated with IFN-β treatment who showed immune regulatory cytokine interleukin (IL)-10 expression. In the disease flare state, we found that PD-1+CD8+ T cells were enriched in the CSF, which predicted a good response to subsequent IV steroid therapy. Transcriptome analysis of sorted PD-1+CD8+ T cells revealed the transcription factor c-Maf as a potential major regulator of the gene module, including multiple coinhibitory molecules. Furthermore, c-Maf expressed in CD8+ T cells induced PD-1 expression and production of IL-10 as well as suppressed alloactivated CD4+ T-cell survival. DISCUSSION: This study uncovered a favorable role of PD-1+CD8+ T cells against MS and demonstrated that c-Maf-driven IL-10 is an immune regulatory machinery.Jul. 2022, Neurology(R) neuroimmunology & neuroinflammation, 9(4) (4), English, International magazineScientific journal
- (一社)日本神経学会, Sep. 2021, 臨床神経学, 61(Suppl.) (Suppl.), S244 - S244, Japanese抗AQP4抗体陽性NMOSD患者末梢血ではB細胞中のDN2の割合が増大し、病勢を反映している
- OBJECTIVES: Cognitive impairment is a common symptom affecting daily activities of the patients with multiple sclerosis (MS). Various cognitive evaluation tests are available, yet most of them are complex and time-consuming to perform in outpatient clinics. In this study, we aimed to validate a Japanese version of the Guy's Neurological Disability Scale (GNDS) as a user-friendly tool to evaluate comprehensive disabilities in MS including cognitive function. METHODS: Questions of the GNDS were translated into Japanese and named GNDS-J. Forty-four patients were examined by the Expanded Disability Status Scale (EDSS), the Paced Auditory Serial Addition Test (PASAT), the Symbol Digit Modalities Test (SDMT), the vitality scale, and the GNDS-J in the same time at remission state. RESULTS: The GNDS-J scores correlated with the EDSS scores(r = 0.61), and inversely correlated with the PASAT2/1(r=-0.56/-0.49) scores and the SDMT scores (r=-0.68), whereas the GNDS-J did not show any correlation with the vitality scale. Furthermore, eleven patients were evaluated over 5 years for changes in these scores. Eight out of 11 patients had exacerbated GNDS, and all of these patients experienced clinical relapse during this period. CONCLUSION: The GNDS-J is a valid tool to perform in outpatient clinics, which could provide a comprehensive scale for evaluating symptoms of MS, thus the disease activity by repeated measure.Oct. 2019, Multiple sclerosis and related disorders, 35, 272 - 275, English, International magazineScientific journal
- We report a patient having classical clinical feature of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and a novel mutation, m.8729 G>A in mitochondria DNA. The patient was referred to our hospital because of progressive ataxia in her limbs and trunk. She had a history of incapability of running long distances from childhood. Neurological examination revealed cerebellar ataxia, distal dominant muscle weakness in the limbs, hyporeflexia, hypoesthesia, myoclonus, sensorineural deafness, and retinitis pigmentosa. Magnetic resonance imaging (MRI) showed atrophy of brain stem and cerebellum as well as calcification of basal ganglia. In both serum and cerebrospinal fluid, lactate and pyruvate levels were elevated. Histological examination of biopsied muscle revealed chronic neurogenic changes without ragged red fibers. Genetic analysis of mitochondrial DNA (mtDNA) of the muscle revealed a heteroplasmic mutation, m.8729 G>A. Chemical analysis of the respiratory chain complexes in her muscle specimen demonstrated lower activities of complexes I and V. In our case, novel mutation of m.8729 G>A in mtDNA was indicated as the cause of NARP syndrome.2015, Rinsho shinkeigaku = Clinical neurology, 55(2) (2), 91 - 5, Japanese, Domestic magazineScientific journal
- (一社)日本神経学会, Mar. 2024, 臨床神経学, 64(3) (3), 227 - 227, Japanese側脳室周囲に造影効果病変を伴った視神経脊髄炎スペクトラム障害(NMOSD)の一例
- (一社)日本神経学会, Mar. 2024, 臨床神経学, 64(3) (3), 230 - 230, Japanese同側顔面および上肢の感覚障害をきたした後脊髄動脈領域梗塞の一例
- 日本画像医学会, Feb. 2024, Japanese Journal of Diagnostic Imaging, 42(増刊) (増刊), 71 - 71, JapaneseMOG抗体関連疾患(MOGAD)の臨床と画像診断 MOG抗体関連疾患の臨床
- (一社)日本臨床免疫学会, Oct. 2023, 日本臨床免疫学会総会プログラム・抄録集, 51回, 64 - 64, Japanese難治性神経免疫疾患 多発性硬化症におけるCD8陽性T細胞の抑制性遺伝子プログラムの解明
- (一社)日本神経学会, Oct. 2023, 臨床神経学, 63(10) (10), 690 - 690, Japaneseてんかん重積を契機として診断された神経梅毒の一例
- (一社)日本神経学会, Sep. 2023, 臨床神経学, 63(Suppl.) (Suppl.), S257 - S257, Japanese非けいれん性てんかん重積における周期性放電の電気生理的転帰関連因子の探索
- (一社)日本神経学会, Sep. 2023, 臨床神経学, 63(Suppl.) (Suppl.), S284 - S284, Japanese結節性硬化症における皮質結節の性状とてんかん性放電の関連
- (一社)日本神経学会, Sep. 2023, 臨床神経学, 63(Suppl.) (Suppl.), S394 - S394, Japanese多発性硬化症の経過中,COVID-19ワクチン接種を契機に1型糖尿病を発症したAPS3型症例
- (一社)日本神経免疫学会, Sep. 2023, 神経免疫学, 28(1) (1), 185 - 185, Japanese多発性硬化症患者脳脊髄液におけるCD8+T細胞上のPD-1発現上昇が良好な長期予後の指標となりうる
- (一社)日本神経免疫学会, Sep. 2023, 神経免疫学, 28(1) (1), 207 - 207, Japanese日本人MSにおける神経障害進行指標としてのSDMTの有用性の検証
- (一社)日本神経学会, Aug. 2023, 臨床神経学, 63(8) (8), 538 - 538, Japanese亜急性の小脳性運動失調から診断されたALK陰性未分化大細胞リンパ腫(ALCL)による傍腫瘍性神経症候群の1例
- (一社)日本神経学会, Aug. 2023, 臨床神経学, 63(8) (8), 543 - 543, Japanese医療連携にて診断から病理解剖(剖検)までを成し遂げたゲルストマン・ストロイスラー・シャインカー病(GSS)の一例
- (一社)日本神経学会, Aug. 2023, 臨床神経学, 63(8) (8), 544 - 544, Japanese脊髄癆で発症した晩期顕性梅毒の36歳男性例
- (一社)日本神経学会, Aug. 2023, 臨床神経学, 63(8) (8), 550 - 550, Japanese右前頭葉焦点切除術後に歩行開始で誘発される強直発作が出現した難治性焦点てんかんの一例
- (一社)日本神経学会, Jun. 2023, 臨床神経学, 63(6) (6), 419 - 419, JapaneseSARS-CoV-2ワクチン接種後に発症した神経痛性筋萎縮症の一例
- (一社)日本神経免疫学会, Oct. 2022, 神経免疫学, 27(1) (1), 122 - 122, Japanese転写因子c-Mafは多発性硬化症におけるCD8+T細胞のPD-1発現を促進し,免疫制御機能を発揮する
- (一社)日本神経免疫学会, Oct. 2022, 神経免疫学, 27(1) (1), 153 - 153, JapaneseNMO2 視神経脊髄炎に対するミコフェノール酸モフェチルによる再発抑制と安全性評価のためのオープン試験
- (一社)日本神経学会, Oct. 2022, 臨床神経学, 62(Suppl.) (Suppl.), S312 - S312, Japanese抗AchR抗体陽性であったが免疫チェックポイント阻害薬を継続できた肺癌の2例
- (一社)日本神経学会, Oct. 2022, 臨床神経学, 62(Suppl.) (Suppl.), S323 - S323, Japanese当院における脊髄硬膜動静脈瘻5例の検討
- 2022, 日本神経学会学術大会プログラム・抄録集, 63rd視神経脊髄炎に対するミコフェノール酸モフェチルによる再発抑制と安全性の評価
- (一社)日本神経免疫学会, Oct. 2021, 神経免疫学, 26(1) (1), 152 - 152, Japaneseペムブロリズマブ投与中に抗アセチルコリン受容体抗体陽性が判明したが治療継続し肺癌の寛解を得た1例
- (一社)日本神経学会, Sep. 2021, 臨床神経学, 61(Suppl.) (Suppl.), S329 - S329, Japanese神経超音波検査が診断に有用だった上腕骨骨折の接合術後に橈骨神経麻痺を発症した2例
- (一社)日本神経学会, Nov. 2020, 臨床神経学, 60(Suppl.) (Suppl.), S328 - S328, JapaneseB細胞の表現型解析は抗AQP4抗体陽性視神経脊髄炎関連疾患と他疾患の鑑別に有用である
- (一社)日本神経学会, Nov. 2020, 臨床神経学, 60(Suppl.) (Suppl.), S329 - S329, Japanese多発性硬化症における変形性脊椎症は脊髄病変と関連する
- 日本神経免疫学会, Oct. 2020, 神経免疫学, 25(1) (1), 105 - 105, JapaneseヘルパーT細胞の共抑制分子発現はMSとNMOの多様性を反映している
- 日本神経免疫学会, Oct. 2020, 神経免疫学, 25(1) (1), 112 - 112, Japanese視神経脊髄炎と類縁疾患の鑑別にB細胞の表現型解析が有用である
- (一社)日本神経免疫学会, Oct. 2020, 神経免疫学, 25(1) (1), 106 - 106, Japanese多発性硬化症における脊髄病変と変形性脊椎症の関連についての検討
- (一社)日本神経学会, Nov. 2019, 臨床神経学, 59(Suppl.) (Suppl.), S319 - S319, JapaneseNMOに対するMMFによる再発抑制と安全性確認のためのオープン試験
- (一社)日本神経学会, Nov. 2019, 臨床神経学, 59(Suppl.) (Suppl.), S277 - S277, Japanese多発性硬化症の急性期治療反応性と相関する脳脊髄液中のPD-1陽性CD8+ T細胞の役割
- (一社)日本神経免疫学会, Sep. 2019, 神経免疫学, 24(1) (1), 150 - 150, Japanese多発性硬化症における制御性CD8+T細胞に関する検討
- (一社)日本神経学会, Dec. 2018, 臨床神経学, 58(Suppl.) (Suppl.), S268 - S268, Japanese日本語版Guy's Neurological Disability Scaleを用いた多発性硬化症の臨床的評価[Refereed]
- (一社)日本神経学会, Dec. 2018, 臨床神経学, 58(Suppl.) (Suppl.), S217 - S217, JapanesePD-1陽性CD8+T細胞は多発性硬化症の治療効果を反映する
- (一社)日本神経免疫学会, Sep. 2018, 神経免疫学, 23(1) (1), 142 - 142, Japanese多発性硬化症におけるPD-1陽性CD8+T細胞の脳脊髄液および末梢血での比較
- (一社)日本神経免疫学会, Oct. 2017, 神経免疫学, 22(1) (1), 95 - 95, JapaneseMS・NMO1 PD-1陽性CD8+T細胞は多発性硬化症の治療効果を反映するバイオマーカーになる
- 日本神経免疫学会, Oct. 2017, 神経免疫学, 22(1) (1), 135 - 135, JapaneseGuy's Neurological Disability Scaleを用いた多発性硬化症の非身体障害機能評価(会議録)Meeting report
- (一社)日本神経学会, Dec. 2016, 臨床神経学, 56(Suppl.) (Suppl.), S392 - S392, Japanese内頸動脈起始部狭窄症例におけるSE法を用いたMRプラークイメージングの臨床的検討
- (一社)日本神経学会, Dec. 2016, 臨床神経学, 56(Suppl.) (Suppl.), S513 - S513, Japanese脳梗塞患者のリハビリテーション評価における生体電気インピーダンス法の有用性の検討
- (一社)日本神経学会, Dec. 2016, 臨床神経学, 56(Suppl.) (Suppl.), S514 - S514, Japanese脳卒中急性期患者の生体電気インピーダンス法を用いた廃用性筋萎縮の経時的評価
- (一社)日本神経学会, Dec. 2016, 臨床神経学, 56(12) (12), 880 - 880, Japaneseけいれん重積に対し長期の全身麻酔を要し、シクロホスファミドパルス療法が奏効した非ヘルペス性辺縁系脳炎の57歳女性例
- (一社)日本神経学会, Sep. 2016, 臨床神経学, 56(9) (9), 652 - 652, Japanese腸炎後に意識障害、両側外眼筋麻痺、両側Babinski徴候を呈し、除皮質硬直肢位から回復した脳幹脳炎の24歳女性例
- (一社)日本神経学会, Dec. 2015, 臨床神経学, 55(Suppl.) (Suppl.), S181 - S181, Japanese高密度表面電極を用いた筋萎縮性側索硬化症における非侵襲的運動単位電位測定[Refereed]
- Nov. 2015, 臨床神経学, 55(11号) (11号), 862, JapaneseMeeting report
- (一社)日本神経学会, Nov. 2015, 臨床神経学, 55(11) (11), 867 - 867, Japanese高IgE血症と重症アトピー性皮膚炎を伴った運動優位型chronic inflammatory demyelinating polyneuropathy(CIDP)の1例
- (一社)日本神経学会, Aug. 2015, 臨床神経学, 55(8号) (8号), 593 - 593, Japanesesensory ganglionopathyと考えられた抗GD1b抗体陽性の59歳女性例Meeting report
- (一社)日本神経学会, Dec. 2014, 臨床神経学, 54(Suppl.) (Suppl.), S199 - S199, Japanese抗GalNAc-GD1a抗体低力価陽性の筋萎縮性側索硬化症に対するIVIgの治療効果[Refereed]
- (一社)日本臨床神経生理学会, Oct. 2014, 臨床神経生理学, 42(5号) (5号), 283 - 283, JapaneseMeeting report
- (一社)日本神経学会, Jan. 2014, 臨床神経学, 54(1) (1), 66 - 66, Japanese意識障害で発症し、MRI拡散強調画像で広範な大脳病変、脳波でPSD様所見を認めた橋本脳症の1例