气候变化领域集成服务门户(CCPortal): Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells

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DOI	10.1073/PNAS.2014043118
	Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells
	Ronin E.; Pouchy C.; Khosravi M.; Hilaire M.; Grégoire S.; Casrouge A.; Kassem S.; Sleurs D.; Martin G.H.; Chanson N.; Lombardi Y.; Lalle G.; Wajant H.; Auffray C.; Lucas B.; Marodon G.; Grinberg-Bleyer Y.; Salomon B.L.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	CD4+Foxp3+ regulatory T (Treg) cells are central modulators of autoimmune diseases. However, the timing and location of Treg cell-mediated suppression of tissue-specific autoimmunity remain undefined. Here, we addressed these questions by investigating the role of tumor necrosis factor (TNF) receptor 2 (TNFR2) signaling in Treg cells during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We found that TNFR2-expressing Treg cells were critical to suppress EAE at peak disease in the central nervous system but had no impact on T cell priming in lymphoid tissues at disease onset. Mechanistically, TNFR2 signaling maintained functional Treg cells with sustained expression of CTLA-4 and Blimp-1, allowing active suppression of pathogenic T cells in the inflamed central nervous system. This late effect of Treg cells was further confirmed by treating mice with TNF and TNFR2 ago-nists and antagonists. Our findings show that endogenous Treg cells specifically suppress an autoimmune disease by acting in the target tissue during overt inflammation. Moreover, they bring a mechanistic insight to some of the adverse effects of anti-TNF therapy in patients. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoimmune diseases; TNF; Treg cells
语种	英语
scopus关键词	B lymphocyte induced maturation protein 1; cytotoxic T lymphocyte antigen 4; tumor necrosis factor; tumor necrosis factor receptor 2; animal cell; animal experiment; animal model; Article; autoimmunity; central nervous system; controlled study; experimental autoimmune encephalomyelitis; lymphoid tissue; mouse; multiple sclerosis; nervous system inflammation; nonhuman; priority journal; protein expression; regulatory T lymphocyte; signal transduction; tissue specificity
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/180049
作者单位	Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI)-Paris, Paris, F-75013, France; Centre de Recherche en Cancérologie de Lyon, Labex DEVweCAN, INSERM, CNRS, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, 69008, France; Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, 97070, Germany; Institut Cochin, CNRS, INSERM, Paris Université, Paris, F-75014, France
推荐引用方式 GB/T 7714	Ronin E.,Pouchy C.,Khosravi M.,et al. Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells[J],2021,118(13).
APA	Ronin E..,Pouchy C..,Khosravi M..,Hilaire M..,Grégoire S..,...&Salomon B.L..(2021).Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Ronin E.,et al."Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).