title: 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-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 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 α (RARα) 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.
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. ruizhuz@stanford.edu
authors.forename: R
authors.initials: R
authors.lastname: Zeng
authors.forename: C
authors.initials: C
authors.lastname: Oderup
authors.forename: R
authors.initials: R
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Habtezion
authors.forename: H
authors.initials: H
authors.lastname: Hadeiba
authors.forename: E C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology*; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D054388:Receptors, CCR / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C119309:CC chemokine receptor 9; D007155:Immunologic Factors; D039001:Integrin alpha Chains; D054388:Receptors, CCR; C091367:alpha E integrins; D039441:Integrin alpha4; D014212:Tretinoin