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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....

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Autores principales: Takahashi, Reiko, Nishimoto, Shuhei, Muto, Go, Sekiya, Takashi, Tamiya, Taiga, Kimura, Akihiro, Morita, Rimpei, Asakawa, Mayako, Chinen, Takatoshi, Yoshimura, Akihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
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.
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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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