Control of TH17 cells occurs in the small intestine.
Control of TH17 cells occurs in the small intestine.
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DOI：
10.1038/nature10228
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发表时间：
2011-07-17
期刊：
影响因子：
64.8
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
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.
产生白细胞介素（IL）-17的T辅助细胞（TH 17）是最近鉴定的不同于T辅助1型（TH 1）和T辅助2型（TH 2）细胞的CD 4 + T细胞亚群。TH 17细胞可以驱动抗原特异性自身免疫性疾病，并且被认为是驱动实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的小鼠模型）的致病性T细胞的主要群体。产生TH 17细胞所需的因子已得到充分表征。然而，免疫系统在体内何处以及如何控制TH 17细胞仍不清楚。在这里，通过使用由CD 3特异性抗体诱导的耐受模型，脓毒症和甲型流感病毒感染（H1N1）的模型，我们表明促炎性TH 17细胞可以被重定向到小肠并在小肠中被控制。TH 17特异性IL-17 A分泌诱导小肠中趋化因子CCL 20的表达，促进这些细胞通过CCR 6/CCL 20轴特异性迁移至小肠。此外，我们发现TH 17细胞在小肠中受到两种不同机制的控制：首先，它们通过肠腔消除，同时促炎TH 17细胞获得具有体外和体内免疫抑制特性的调节表型（rTH 17）。这些结果确定了限制TH 17细胞致病性的机制，并暗示胃肠道是控制TH 17细胞的部位。
Interleukin (IL)-17-producing T helper cells (TH17) are a recently identified CD4+ T cell subset distinct from T helper type 1 (TH1) and T helper type 2 (TH2) cells. TH17 cells can drive antigen specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. The factors that are needed for the generation of TH17 cells have been well-characterized. However, where and how the immune system controls TH17 cells in vivo remains unclear. Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory TH17 cells can be redirected to and controlled in the small intestine. TH17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that TH17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen and simultaneously pro-inflammatory TH17 cells acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rTH17). These results identify mechanisms limiting TH17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of TH17 cells.
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DOI：
10.1016/j.clim.2009.04.007
发表时间：
2009-08
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Herold KC;Gitelman S;Greenbaum C;Puck J;Hagopian W;Gottlieb P;Sayre P;Bianchine P;Wong E;Seyfert-Margolis V;Bourcier K;Bluestone JA;Immune Tolerance Network ITN007AI Study Group
通讯作者：
Immune Tolerance Network ITN007AI Study Group
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
Reboldi, Andrea;Coisne, Caroline;Sallusto, Federica
通讯作者：
Sallusto, Federica