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Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells.

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-?DCs). Pre-?DCs express the gut trafficking receptor ?4?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-?DCs in vivo in the BM or in vitro is regulated by RA and RA receptor ? (RAR?) signaling. The frequency of pre-?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.

SUBMITTER: Zeng R

PROVIDER: S-EPMC3612556 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells.

Zeng R R Oderup C C Yuan R R Lee M M Habtezion A A Hadeiba H H Butcher E C EC

Mucosal immunology 20121212 4

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 α4β7 and home preferentially to the intestines. They develop in the bone marrow (BM), can differentiate into CCR9⁺ plasmacytoid DCs as well as convention ...[more]

PMID: 23235743

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