Apoptosis in response to microbial infection induces autoreactive TH17 cells.
Apoptosis in response to microbial infection induces autoreactive TH17 cells.
复制标题
响应微生物感染的凋亡诱导自动反应性TH17细胞。
作者：
微生物感染往往先于自身免疫的发生。感染如何触发自身免疫仍然知之甚少。我们研究了感染可能会创造条件，允许自我肽本身的刺激性介绍，这可能足以引起自身反应性T细胞反应，导致自身免疫的可能性。自身反应性CD4+ T细胞是自身免疫性疾病的主要驱动因素，但它们的活化通常通过限制自身抗原的免疫刺激呈递的调节机制来阻止。在这里，我们发现，受感染的宿主细胞的凋亡，使介绍自身抗原的主要组织相容性复合物II类分子在炎症的情况下。这足以产生辅助性T细胞的自身反应性TH17亚群，与自身免疫性疾病显著相关。一旦被诱导，自身反应性TH17细胞促进自身炎症和自身抗体产生。我们的研究结果对感染如何促进自身免疫有一定的意义。
Microbial infections often precede the onset of autoimmunity. How infections trigger autoimmunity remains poorly understood. We investigated the possibility that infection might create conditions that allow the stimulatory presentation of self peptides themselves and that this might suffice to elicit autoreactive T cell responses that lead to autoimmunity. Self-reactive CD4+ T cells are major drivers of autoimmune disease, but their activation is normally prevented through regulatory mechanisms that limit the immune-stimulatory presentation of self antigens. Here we found that the apoptosis of infected host cells enabled the presentation of self antigens by major histocompatibility complex class II molecules in an inflammatory context. This was sufficient for the generation of an autoreactive TH17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive TH17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity.
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影响因子：
32.4
作者：
Legoux FP;Lim JB;Cauley AW;Dikiy S;Ertelt J;Mariani TJ;Sparwasser T;Way SS;Moon JJ
通讯作者：
Moon JJ
影响因子：
64.8
作者：
Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
82.9
作者：
Cho JH;Feldman M
通讯作者：
Feldman M
影响因子：
7.8
作者：
Kleinewietfeld M;Hafler DA
通讯作者：
Hafler DA