2012年9月
Dietary Folic Acid Promotes Survival of Foxp3(+) Regulatory T Cells in the Colon
JOURNAL OF IMMUNOLOGY
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- 巻
- 189
- 号
- 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
- ID情報
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- DOI : 10.4049/jimmunol.1200420
- ISSN : 0022-1767
- PubMed ID : 22869901
- Web of Science ID : WOS:000308698600023