气候变化领域集成服务门户(CCPortal): Involvement of cytotoxic Eomes-expressing CD4+T cells in secondary progressive multiple sclerosis

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DOI	10.1073/pnas.2021818118
	Involvement of cytotoxic Eomes-expressing CD4+T cells in secondary progressive multiple sclerosis
	Raveney B.J.E.; Sato W.; Takewaki D.; Zhang C.; Kanazawa T.; Lin Y.; Okamoto T.; Araki M.; Kimura Y.; Sato N.; Sano T.; Saito Y.; Oki S.; Yamamura T.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	Multiple sclerosis (MS), a putative autoimmune disease of the central nervous system (CNS), commonly presents as relapsing-remitting MS (RRMS), characterized by recurrent episodes of peripheral disabling symptoms resulting from inflammatory CNS damage. Many RRMS patients transition to a chronic disease course with progressive neurological dysfunctions (secondary progressive MS, SPMS), with the progression rate varying between patients and over time. SPMS pathogenesis is now linked to immune-cell-mediated processes, although the mechanisms driving SPMS transition and progression remain elusive, and SPMS lacks biomarkers and effective treatments. We report the crucial involvement of cytotoxic CD4+T cells expressing Eomes (Eomes+Th cells) in SPMS pathogenesis-a Th cell subset previously identified in a mouse model of late/chronic autoimmune CNS inflammation. Few Eomes+Th cells circulate in RRMS patient peripheral blood (n = 44), primary progressive MS (PPMS) patients (n = 25), or healthy controls (n = 42), but Eomes+Th cells were significantly increased in SPMS (n = 105, P < 0.0001). Strikingly, lymphocytes isolated from SPMS autopsy brain samples revealed CD4+T cells infiltrating CNS that coexpressed Eomes and the cytotoxic molecule granzyme B. In particular, the Eomes+Th cell levels were increased in SPMS patients in progressive disease phases versus SPMS patients without current disability increases (P < 0.0001). Moreover, Eomes level acted as a biomarker to predict SPMS patients at risk of diseaseworsening with over 80% accuracy (ROC-AUC = 0.8276). Overall, our results indicate that granzyme B-expressing Eomes+T helper cells are involved in the pathogenesis of SPMS, with significant implications for SPMS biomarkers and therapeutic targets. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoimmunity; Biomarkers; Eomes+ Th cells; Multiple sclerosis; Secondary progressive multiple sclerosis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180257
作者单位	Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan; Multiple Sclerosis Center, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8551, Japan; Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8551, Japan; Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8551, Japan; Department of Pathology and Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8551, Japan
推荐引用方式 GB/T 7714	Raveney B.J.E.,Sato W.,Takewaki D.,et al. Involvement of cytotoxic Eomes-expressing CD4+T cells in secondary progressive multiple sclerosis[J],2021,118(11).
APA	Raveney B.J.E..,Sato W..,Takewaki D..,Zhang C..,Kanazawa T..,...&Yamamura T..(2021).Involvement of cytotoxic Eomes-expressing CD4+T cells in secondary progressive multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Raveney B.J.E.,et al."Involvement of cytotoxic Eomes-expressing CD4+T cells in secondary progressive multiple sclerosis".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).