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Abstract
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-µDCs). Pre-µDCs express the gut trafficking receptor a4ß7 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-µDCs in vivo in the BM or in vitro is regulated by RA and RA receptor a (RARa) signaling. The frequency of pre-µDCs 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.
View details for DOI 10.1038/mi.2012.123
View details for PubMedID 23235743
View details for PubMedCentralID PMC3612556