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 |
|---|---|
| Journal | Nature Communications |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
AU - Chinen, Takatoshi
AU - Komai, Kyoko
AU - Muto, Go
AU - Morita, Rimpei
AU - Inoue, Naoko
AU - Yoshida, Hideyuki
AU - Sekiya, Takashi
AU - Yoshida, Ryoko
AU - Nakamura, Kazuhiko
AU - Takayanagi, Ryoichi
AU - Yoshimura, Akihiko
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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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U2 - 10.1038/ncomms1181
DO - 10.1038/ncomms1181
M3 - Article
VL - 2
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
ER -