Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance.

Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance.
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DOI:
10.1038/ncomms1181
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发表时间:
2011-02-08
影响因子:
16.6
通讯作者:
Yoshimura A
Yoshimura A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chinen T;Komai K;Muto G;Morita R;Inoue N;Yoshida H;Sekiya T;Yoshida R;Nakamura K;Takayanagi R;Yoshimura A

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白细胞介素10(IL-10)和调节性T细胞(Tcells)维持对肠道微生物的耐受性。然而,缺乏IL-10和Tcl 3的Il 10 −/− Rag 2 −/−小鼠仍然健康,这表明存在其他耐受机制。在这里,我们确定细胞因子信号转导抑制因子1(SOCS 1)作为肠道免疫耐受的重要介质。Socs 1 −/− Rag 2 −/−小鼠会发生严重的结肠炎,这可以通过减少微生物群和转移IL-10充足的TcR来预防。此外,我们发现前列腺素E2(PGE 2)在维持肠内的耐受性中起着重要作用。Socs 1 −/−树突状细胞对PGE 2介导的免疫抑制有抵抗力,因为细胞因子信号失调。因此,我们建议SOCS 1和PGE 2,潜在地相互作用在一起,作为一种替代的肠耐受机制不同于IL-10和TGE 2。肠道中有无数的微生物,免疫系统如何耐受它们的存在是非常有趣的。在这里,通过研究多基因敲除小鼠的结肠形态,作者证明了前列腺素E2和SOCS 1在介导免疫耐受中的潜在作用。
Interleukin 10 (IL-10) and regulatory T cells (Tregs) maintain tolerance to intestinal microorganisms. However, Il10−/−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. The gut is populated by a myriad of microorganisms and how the immune system tolerates their presence is of great interest. Here, by studying colon morphology in multiple knockout mice, the authors demonstrate a potential role for prostaglandin E2 and SOCS1 in mediating immune tolerance.
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