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Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance

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...

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Autores principales: Chinen, Takatoshi, Komai, Kyoko, Muto, Go, Morita, Rimpei, Inoue, Naoko, Yoshida, Hideyuki, Sekiya, Takashi, Yoshida, Ryoko, Nakamura, Kazuhiko, Takayanagi, Ryoichi, Yoshimura, Akihiko
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105338/
https://www.ncbi.nlm.nih.gov/pubmed/21304519
http://dx.doi.org/10.1038/ncomms1181
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author Chinen, Takatoshi
Komai, Kyoko
Muto, Go
Morita, Rimpei
Inoue, Naoko
Yoshida, Hideyuki
Sekiya, Takashi
Yoshida, Ryoko
Nakamura, Kazuhiko
Takayanagi, Ryoichi
Yoshimura, Akihiko
author_facet Chinen, Takatoshi
Komai, Kyoko
Muto, Go
Morita, Rimpei
Inoue, Naoko
Yoshida, Hideyuki
Sekiya, Takashi
Yoshida, Ryoko
Nakamura, Kazuhiko
Takayanagi, Ryoichi
Yoshimura, Akihiko
author_sort Chinen, Takatoshi
collection PubMed
description 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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spelling pubmed-31053382011-06-01 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 Nat Commun Article 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. Nature Publishing Group 2011-02-08 /pmc/articles/PMC3105338/ /pubmed/21304519 http://dx.doi.org/10.1038/ncomms1181 Text en Copyright © 2011, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
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
title Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
title_full Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
title_fullStr Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
title_full_unstemmed Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
title_short Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
title_sort prostaglandin e2 and socs1 have a role in intestinal immune tolerance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105338/
https://www.ncbi.nlm.nih.gov/pubmed/21304519
http://dx.doi.org/10.1038/ncomms1181
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