IL-27 promotes T cell-dependent colitis through multiple mechanisms.
IL-27 promotes T cell-dependent colitis through multiple mechanisms.
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DOI：
10.1084/jem.20100410
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发表时间：
2011-01-17
期刊：
影响因子：
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通讯作者：
Ghilardi N
中科院分区：
文献类型：
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作者：
Cox JH;Kljavin NM;Ramamoorthi N;Diehl L;Batten M;Ghilardi N
缺乏IL-27受体的T细胞在小鼠中产生不太严重的结肠炎，并且更容易上调Foxp 3表达。白细胞介素-27（IL-27）是已知具有促炎和免疫调节功能的细胞因子。后者似乎在体内占主导地位，其中IL-27抑制TH 17应答并促进表达干扰素-γ和IL-10且缺乏叉头框P3（Foxp 3）的Tr 1细胞的分化。因此，IL-27受体α（IL-27 ra）缺陷型小鼠在感染各种寄生虫或用自身抗原攻击时，免疫病理学恶化。由于IL-27在人类和实验小鼠结肠炎中的作用是有争议的，我们研究了IL-27 ra缺失在结肠炎小鼠T细胞转移模型中的后果，意外地发现了IL-27的促炎作用。转移的T细胞上缺乏Il 27 ra导致体重减轻减少和结肠炎症减少。更大比例的转移的T细胞在不存在IL-27 ra的情况下呈现Foxp 3+表型，表明IL-27的功能是抑制调节性T细胞（Treg）发育。事实上，IL-27在体外和在卵清蛋白依赖性耐受化模型中抑制Foxp 3诱导。此外，在不存在Il 27 ra的情况下，效应细胞增殖和IFN-γ产生减少。总的来说，我们描述了IL-27在T细胞依赖性肠道炎症中的促炎作用，并提供了在外周免疫耐受崩溃导致的病理情况下靶向这种细胞因子的基本原理。
T cells lacking the IL-27 receptor generate less severe colitis in mice, and more readily up-regulate Foxp3 expression. Interleukin-27 (IL-27) is a cytokine known to have both proinflammatory and immunoregulatory functions. The latter appear to dominate in vivo, where IL-27 suppresses TH17 responses and promotes the differentiation of Tr1 cells expressing interferon-γ and IL-10 and lacking forkhead box P3 (Foxp3). Accordingly, IL-27 receptor α (Il27ra)–deficient mice suffer from exacerbated immune pathology when infected with various parasites or challenged with autoantigens. Because the role of IL-27 in human and experimental mouse colitis is controversial, we studied the consequences of Il27ra deletion in the mouse T cell transfer model of colitis and unexpectedly discovered a proinflammatory role of IL-27. Absence of Il27ra on transferred T cells resulted in diminished weight loss and reduced colonic inflammation. A greater fraction of transferred T cells assumed a Foxp3+ phenotype in the absence of Il27ra, suggesting that IL-27 functions to restrain regulatory T cell (Treg) development. Indeed, IL-27 suppressed Foxp3 induction in vitro and in an ovalbumin-dependent tolerization model in vivo. Furthermore, effector cell proliferation and IFN-γ production were reduced in the absence of Il27ra. Collectively, we describe a proinflammatory role of IL-27 in T cell–dependent intestinal inflammation and provide a rationale for targeting this cytokine in pathological situations that result from a breakdown in peripheral immune tolerance.
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影响因子：
30.8
作者：
Imielinski, Marcin;Baldassano, Robert N.;Griffiths, Anne;Russell, Richard K.;Annese, Vito;Dubinsky, Marla;Kugathasan, Subra;Bradfield, Jonathan P.;Walters, Thomas D.;Sleiman, Patrick;Kim, Cecilia E.;Muise, Aleixo;Wang, Kai;Glessner, Joseph T.;Saeed, Shehzad;Zhang, Haitao;Frackelton, Edward C.;Hou, Cuiping;Flory, James H.;Otieno, George;Chiavacci, Rosetta M.;Grundmeier, Robert;Castro, Massimo;Latiano, Anna;Dallapiccola, Bruno;Stempak, Joanne;Abrams, Debra J.;Taylor, Kent;McGovern, Dermot;Heyman, Melvin B.;Ferry, George D.;Kirschner, Barbara;Lee, Jessica;Essers, Jonah;Grand, Richard;Stephens, Michael;Levine, Arie;Piccoli, David;Van Limbergen, Johan;Cucchiara, Salvatore;Monos, Dimitri S.;Guthery, Stephen L.;Denson, Lee;Wilson, David C.;Grant, Struan F. A.;Daly, Mark;Silverberg, Mark S.;Satsangi, Jack;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
32.4
作者：
Pflanz, S;Timans, JC;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
4.4
作者：
POWRIE, F;LEACH, MW;COFFMAN, RL
通讯作者：
COFFMAN, RL
影响因子：
64.8
作者：
Chen, Q;Ghilardi, N;de Sauvage, FJ
通讯作者：
de Sauvage, FJ
影响因子：
30.5
作者：
通讯作者：
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