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SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production
Regulatory T cells (T(reg) cells) maintain immune homeostasis by limiting inflammatory responses. SOCS1 (suppressor of cytokine signaling 1), a negative regulator of cytokine signaling, is necessary for the suppressor functions of T(reg) cells in vivo, yet detailed mechanisms remain to be clarified....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182063/ https://www.ncbi.nlm.nih.gov/pubmed/21893603 http://dx.doi.org/10.1084/jem.20110428 |
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author | Takahashi, Reiko Nishimoto, Shuhei Muto, Go Sekiya, Takashi Tamiya, Taiga Kimura, Akihiro Morita, Rimpei Asakawa, Mayako Chinen, Takatoshi Yoshimura, Akihiko |
author_facet | Takahashi, Reiko Nishimoto, Shuhei Muto, Go Sekiya, Takashi Tamiya, Taiga Kimura, Akihiro Morita, Rimpei Asakawa, Mayako Chinen, Takatoshi Yoshimura, Akihiko |
author_sort | Takahashi, Reiko |
collection | PubMed |
description | Regulatory T cells (T(reg) cells) maintain immune homeostasis by limiting inflammatory responses. SOCS1 (suppressor of cytokine signaling 1), a negative regulator of cytokine signaling, is necessary for the suppressor functions of T(reg) cells in vivo, yet detailed mechanisms remain to be clarified. We found that Socs1(−/−) T(reg) cells produced high levels of IFN-γ and rapidly lost Foxp3 when transferred into Rag2(−/−) mice or cultured in vitro, even though the CNS2 (conserved noncoding DNA sequence 2) in the Foxp3 enhancer region was fully demethylated. Socs1(−/−) T(reg) cells showed hyperactivation of STAT1 and STAT3. Because Foxp3 expression was stable and STAT1 activation was at normal levels in Ifnγ(−/−)Socs1(−/−) T(reg) cells, the restriction of IFN-γ–STAT1 signaling by SOCS1 is suggested to be necessary for stable Foxp3 expression. However, Ifnγ(−/−)Socs1(−/−) T(reg) cells had hyperactivated STAT3 and higher IL-17A (IL-17) production compared with Ifnγ(−/−)Socs1(+/+) T(reg) cells and could not suppress colitis induced by naive T cells in Rag2(−/−) mice. In vitro experiments suggested that cytokines produced by Socs1(−/−) T(reg) cells and Ifnγ(−/−)Socs1(−/−) T(reg) cells modulated antigen-presenting cells for preferential Th1 and Th17 induction, respectively. We propose that SOCS1 plays important roles in T(reg) cell integrity and function by maintaining Foxp3 expression and by suppressing IFN-γ and IL-17 production driven by STAT1 and STAT3, respectively. |
format | Online Article Text |
id | pubmed-3182063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31820632012-03-26 SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production Takahashi, Reiko Nishimoto, Shuhei Muto, Go Sekiya, Takashi Tamiya, Taiga Kimura, Akihiro Morita, Rimpei Asakawa, Mayako Chinen, Takatoshi Yoshimura, Akihiko J Exp Med Article Regulatory T cells (T(reg) cells) maintain immune homeostasis by limiting inflammatory responses. SOCS1 (suppressor of cytokine signaling 1), a negative regulator of cytokine signaling, is necessary for the suppressor functions of T(reg) cells in vivo, yet detailed mechanisms remain to be clarified. We found that Socs1(−/−) T(reg) cells produced high levels of IFN-γ and rapidly lost Foxp3 when transferred into Rag2(−/−) mice or cultured in vitro, even though the CNS2 (conserved noncoding DNA sequence 2) in the Foxp3 enhancer region was fully demethylated. Socs1(−/−) T(reg) cells showed hyperactivation of STAT1 and STAT3. Because Foxp3 expression was stable and STAT1 activation was at normal levels in Ifnγ(−/−)Socs1(−/−) T(reg) cells, the restriction of IFN-γ–STAT1 signaling by SOCS1 is suggested to be necessary for stable Foxp3 expression. However, Ifnγ(−/−)Socs1(−/−) T(reg) cells had hyperactivated STAT3 and higher IL-17A (IL-17) production compared with Ifnγ(−/−)Socs1(+/+) T(reg) cells and could not suppress colitis induced by naive T cells in Rag2(−/−) mice. In vitro experiments suggested that cytokines produced by Socs1(−/−) T(reg) cells and Ifnγ(−/−)Socs1(−/−) T(reg) cells modulated antigen-presenting cells for preferential Th1 and Th17 induction, respectively. We propose that SOCS1 plays important roles in T(reg) cell integrity and function by maintaining Foxp3 expression and by suppressing IFN-γ and IL-17 production driven by STAT1 and STAT3, respectively. The Rockefeller University Press 2011-09-26 /pmc/articles/PMC3182063/ /pubmed/21893603 http://dx.doi.org/10.1084/jem.20110428 Text en © 2011 Takahashi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Takahashi, Reiko Nishimoto, Shuhei Muto, Go Sekiya, Takashi Tamiya, Taiga Kimura, Akihiro Morita, Rimpei Asakawa, Mayako Chinen, Takatoshi Yoshimura, Akihiko SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title | SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title_full | SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title_fullStr | SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title_full_unstemmed | SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title_short | SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production |
title_sort | socs1 is essential for regulatory t cell functions by preventing loss of foxp3 expression as well as ifn-γ and il-17a production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182063/ https://www.ncbi.nlm.nih.gov/pubmed/21893603 http://dx.doi.org/10.1084/jem.20110428 |
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