Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production.
Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production.
复制标题
DOI：
10.4049/jimmunol.1001454
复制
发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Feng T;Qin H;Wang L;Benveniste EN;Elson CO;Cong Y
Th 1和Th 17细胞都参与了炎症性肠病（IBD）和实验性结肠炎的发病机制。然而，Th 1和Th 17细胞之间的复杂关系及其在IBD发病机制中的相对作用尚未完全分析。虽然最近已经表明，Th 17细胞可以转化为Th 1细胞，但在结肠炎的发病机制中，由Th 17细胞转化为Th 1细胞的潜在体内机制和作用仍然很大程度上未知。我们在这里报告说，来自CBir 1 TCR转基因小鼠的Th 17细胞，对免疫显性微生物群抗原具有特异性，在诱导结肠炎方面比Th 1细胞更有效，因为Th 17细胞诱导严重的结肠炎，而Th 1细胞在转移到TCRβxδ−/−小鼠时诱导轻度结肠炎。Th 17细胞受体结肠内IL-12和IL-23水平升高，IFNγ+ Th 1细胞数量增多。给予抗IL-17单克隆抗体可消除Th 17细胞诱导的结肠炎发展，阻断结肠IL-12和IL-23的产生，并抑制IFNγ+ Th 1细胞的诱导/转化。IL-17促进树突状细胞产生IL-12和IL-23。此外，来自结肠炎Th 17细胞受体的结肠组织的条件培养基诱导Th 17细胞产生IFNγ，其被IL-12和IL-23的阻断所抑制。总的来说，这些数据表明Th 17细胞通过IL-17诱导粘膜先天IL-12和IL-23产生而转化为Th 1细胞。
Both Th1 and Th17 cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) and experimental colitis. However, the complex relationship between Th1 and Th17 cells and their relative contributions to the pathogenesis of IBD have not been completely analyzed. Although it has been recently shown that Th17 cells can convert into Th1 cells, the underlying in vivo mechanisms and the role of Th1 cells converted from Th17 cells in the pathogenesis of colitis are still largely unknown. We report here that Th17 cells from CBir1 TCR transgenic mice, which are specific for an immunodominant microbiota antigen, are more potent than Th1 cells in the induction of colitis, as Th17 cells induced severe colitis, whereas Th1 cells induced mild colitis when transferred into TCRβxδ−/− mice. High levels of IL-12 and IL-23, and substantial numbers of IFNγ+ Th1 cells emerged in the colons of Th17 cell recipients. Administration of anti-IL-17 monoclonal antibody abrogated Th17 cell-induced colitis development, blocked colonic IL-12 and IL-23 production, and inhibited IFNγ+ Th1 cell induction/conversion. IL-17 promoted dendritic cell production of IL-12 and IL-23. Furthermore, conditioned media from colonic tissues of colitic Th17 cell recipients induced IFNγ production by Th17 cells, which was inhibited by blockade of IL-12 and IL-23. Collectively, these data indicate that Th17 cells convert to Th1 cells through IL-17 induction of mucosal innate IL-12 and IL-23 production.
登录
查看更多内容
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
溃疡性结肠炎中克罗恩病风险的研究进一步定义了它们的分子关系。
影响因子：
29.4
作者：
Anderson CA;Massey DC;Barrett JC;Prescott NJ;Tremelling M;Fisher SA;Gwilliam R;Jacob J;Nimmo ER;Drummond H;Lees CW;Onnie CM;Hanson C;Blaszczyk K;Ravindrarajah R;Hunt S;Varma D;Hammond N;Lewis G;Attlesey H;Watkins N;Ouwehand W;Strachan D;McArdle W;Lewis CM;Wellcome Trust Case Control Consortium;Lobo A;Sanderson J;Jewell DP;Deloukas P;Mansfield JC;Mathew CG;Satsangi J;Parkes M
通讯作者：
Parkes M
影响因子：
29.4
作者：
Feng T;Cao AT;Weaver CT;Elson CO;Cong Y
通讯作者：
Cong Y
DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者：
Cong Y
DOI：
10.1084/jem.20100052
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lochner M;Ohnmacht C;Presley L;Bruhns P;Si-Tahar M;Sawa S;Eberl G
通讯作者：
Eberl G