Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance

被引：101

作者：

Chinen, Takatoshi ^{[1
,2
]}

Komai, Kyoko ^{[1
,3
]}

Muto, Go ^{[1
,3
]}

Morita, Rimpei ^{[1
,3
]}

Inoue, Naoko ^{[1
,3
]}

Yoshida, Hideyuki ^{[1
,3
]}

Sekiya, Takashi ^{[1
,3
]}

Yoshida, Ryoko ^{[1
,3
]}

Nakamura, Kazuhiko ^{[2
]}

Takayanagi, Ryoichi ^{[2
]}

Yoshimura, Akihiko ^{[1
,3
]}

机构：

[1] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 8128582, Japan

[3] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo 1020075, Japan

来源：

NATURE COMMUNICATIONS | 2011年 / 2卷

关键词：

INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; CROHNS-DISEASE; IFN-GAMMA; CHRONIC ENTEROCOLITIS; CYTOKINE SIGNALING-1; DENDRITIC CELLS; B-CELLS;

D O I：

10.1038/ncomms1181

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Interleukin 10 (IL-10) and regulatory T cells (Tregs) maintain tolerance to intestinal microorganisms. However, //10(-/-) Rag2(-/-) mice, which lack IL-10 and Tregs, remain healthy, suggesting the existence of other mechanisms of tolerance. Here, we identify suppressor of cytokine signalling 1 (SOCS1) as an essential mediator of immune tolerance in the intestine. Socs1(-/-) Rag2(-/-) mice develop severe colitis, which can be prevented by the reduction of microbiota and the transfer of IL-10-sufficient Tregs. Additionally, we find an essential role for prostaglandin E2 (PGE2) in the maintenance of tolerance within the intestine in the absence of Tregs. Socs1(-/-) dendritic cells are resistant to PGE2-mediated immunosuppression because of dysregulated cytokine signalling. Thus, we propose that SOCS1 and PGE2, potentially interacting together, act as an alternative intestinal tolerance mechanism distinct from IL-10 and Tregs.

引用

页数：11

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