期刊
MUCOSAL IMMUNOLOGY
卷 6, 期 4, 页码 847-856出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2012.123
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类别
资金
- National Science Scholarship
- Agency for Science, Technology And Research, Singapore
- Wenner-Gren Foundation
- Crohn's & Colitis Foundation of America [2791]
- Immunology training Grant [5 T32 AI07290]
- Crohn's and Colitis Foundation
- NIH [AI07290, DK085426, AI047822, AI093981, DK084647]
- Arthritis Foundation
- FACS Core facility of the Stanford Digestive Disease Center [DK056339]
- Department of Veterans Affairs
The vitamin A metabolite retinoic acid (RA) regulates intestinal immune responses through immunomodulatory actions on intestinal dendritic cells (DCs) and lymphocytes. Here, we show that RA also controls the generation of gut-tropic migratory DC precursors, referred to as pre-mucosal DCs (pre-mu DCs). Pre-mu DCs express the gut trafficking receptor alpha 4 beta 7 and home preferentially to the intestines. They develop in the bone marrow (BM), can differentiate into CCR9(+) plasmacytoid DCs as well as conventional DCs (cDCs), but preferentially give rise to CD103(+) intestinal cDCs. Generation of pre-mu DCs in vivo in the BM or in vitro is regulated by RA and RA receptor alpha (RAR alpha) signaling. The frequency of pre-mu DCs is reduced in vitamin A-deficient animals and in animals treated with RAR inhibitors. The results define a novel vitamin A-dependent, RA-regulated developmental sequence for DCs and identify a targeted precursor for CD103(+) cDCs in the gut.
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