論文

査読有り
2012年9月

Dietary Folic Acid Promotes Survival of Foxp3(+) Regulatory T Cells in the Colon

JOURNAL OF IMMUNOLOGY
  • Makoto Kinoshita
  • ,
  • Hisako Kayama
  • ,
  • Takashi Kusu
  • ,
  • Tomoyuki Yamaguchi
  • ,
  • Jun Kunisawa
  • ,
  • Hiroshi Kiyono
  • ,
  • Shimon Sakaguchi
  • ,
  • Kiyoshi Takeda

189
6
開始ページ
2869
終了ページ
2878
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4049/jimmunol.1200420
出版者・発行元
AMER ASSOC IMMUNOLOGISTS

Dietary compounds as well as commensal microbiota contribute to the generation of a unique gut environment. In this study, we report that dietary folic acid (FA) is required for the maintenance of Foxp3(+) regulatory T cells (Tregs) in the colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3(+) Tregs selectively in the colon. Blockade of folate receptor 4 and treatment with methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3(+) Tregs. Compared with splenic Tregs, colonic Tregs were more activated to proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs derived from mice fed with a FA-deficient diet, expression of anti-apoptotic molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further decrease by additional FA deficiency was observed exclusively in the colon. Mice fed with an FA-deficient diet exhibited higher susceptibility to intestinal inflammation. These findings reveal the previously unappreciated role of dietary FA in promotion of survival of Foxp3(+) Tregs that are in a highly activated state in the colon. The Journal of Immunology, 2012, 189: 2869-2878.

リンク情報
DOI
https://doi.org/10.4049/jimmunol.1200420
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22869901
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000308698600023&DestApp=WOS_CPL
ID情報
  • DOI : 10.4049/jimmunol.1200420
  • ISSN : 0022-1767
  • PubMed ID : 22869901
  • Web of Science ID : WOS:000308698600023

エクスポート
BibTeX RIS