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

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68 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 languageEnglish
Article number190
JournalNature communications
Volume2
Issue number1
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

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

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    Chinen, T., Komai, K., Muto, G., Morita, R., Inoue, N., Yoshida, H., Sekiya, T., Yoshida, R., Nakamura, K., Takayanagi, R., & Yoshimura, A. (2011). Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. Nature communications, 2(1), [190]. https://doi.org/10.1038/ncomms1181