Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance

Takatoshi Chinen; Kyoko Komai; Go Muto; Rimpei Morita; Naoko Inoue; Hideyuki Yoshida; Takashi Sekiya; Ryoko Yoshida; Kazuhiko Nakamura; Ryoichi Takayanagi; Akihiko Yoshimura

doi:10.1038/ncomms1181

Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance

Takatoshi Chinen, Kyoko Komai, Go Muto, Rimpei Morita, Naoko Inoue, Hideyuki Yoshida, Takashi Sekiya, Ryoko Yoshida, Kazuhiko Nakamura, Ryoichi Takayanagi, Akihiko Yoshimura

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

71 Citations (Scopus)

Abstract

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.

Original language	English
Article number	190
Journal	Nature communications
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/ncomms1181
Publication status	Published - 2011

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. / Chinen, Takatoshi; Komai, Kyoko; Muto, Go; Morita, Rimpei; Inoue, Naoko; Yoshida, Hideyuki; Sekiya, Takashi; Yoshida, Ryoko; Nakamura, Kazuhiko; Takayanagi, Ryoichi; Yoshimura, Akihiko.

In: Nature communications, Vol. 2, No. 1, 190, 2011.

Research output: Contribution to journal › Article › peer-review

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abstract = "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.",

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AU - Yoshida, Hideyuki

AU - Sekiya, Takashi

AU - Yoshida, Ryoko

AU - Nakamura, Kazuhiko

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AU - Yoshimura, Akihiko

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Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance

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