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
C2 - 21304519
AN - SCOPUS:79851469416
VL - 2
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 190
ER -