論文

査読有り
2011年9月

SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-gamma and IL-17A production

JOURNAL OF EXPERIMENTAL MEDICINE
  • Reiko Takahashi
  • ,
  • Shuhei Nishimoto
  • ,
  • Go Muto
  • ,
  • Takashi Sekiya
  • ,
  • Taiga Tamiya
  • ,
  • Akihiro Kimura
  • ,
  • Rimpei Morita
  • ,
  • Mayako Asakawa
  • ,
  • Takatoshi Chinen
  • ,
  • Akihiko Yoshimura

208
10
開始ページ
2055
終了ページ
2067
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1084/jem.20110428
出版者・発行元
ROCKEFELLER UNIV PRESS

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-gamma 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 Ifn gamma(-/-)Socs1(-/-) T(reg) cells, the restriction of IFN-gamma-STAT1 signaling by SOCS1 is suggested to be necessary for stable Foxp3 expression. However, Ifn gamma(-/-)Socs1(-/-) T(reg) cells had hyper-activated STAT3 and higher IL-17A (IL-17) production compared with Ifn gamma(-/-)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 Ifn gamma(-/-)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-gamma and IL-17 production driven by STAT1 and STAT3, respectively.

Web of Science ® 被引用回数 : 110

リンク情報
DOI
https://doi.org/10.1084/jem.20110428
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21893603
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000295318900012&DestApp=WOS_CPL

エクスポート
BibTeX RIS