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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalNature Communications
Volume2
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint

prostaglandins
interleukins
suppressors
Immune Tolerance
Dinoprostone
Interleukin-10
Cytokines
intestines
mice
immunosuppression
Intestines
microorganisms
T-cells
maintenance
Microbiota
Regulatory T-Lymphocytes
Colitis
Microorganisms
Immunosuppression
Dendritic Cells

ASJC Scopus subject areas

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

Cite this

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, 2011.

Research output: Contribution to journalArticle

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, vol. 2, no. 1. https://doi.org/10.1038/ncomms1181
Chinen, Takatoshi ; Komai, Kyoko ; Muto, Go ; Morita, Rimpei ; Inoue, Naoko ; Yoshida, Hideyuki ; Sekiya, Takashi ; Yoshida, Ryoko ; Nakamura, Kazuhiko ; Takayanagi, Ryoichi ; Yoshimura, Akihiko. / Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. In: Nature Communications. 2011 ; Vol. 2, No. 1.
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AU - Yoshida, Hideyuki

AU - Sekiya, Takashi

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