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

Mucosal Immunol. 2013 Jul;6(4):847-56. doi: 10.1038/mi.2012.123. Epub 2012 Dec 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism*
  • Immunologic Factors / pharmacology*
  • Immunophenotyping
  • Integrin alpha Chains / metabolism
  • Integrin alpha4 / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Mice
  • Peyer's Patches / drug effects
  • Peyer's Patches / immunology
  • Peyer's Patches / metabolism
  • Phenotype
  • Receptors, CCR / metabolism
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism*
  • Tretinoin / pharmacology*


  • Antigens, CD
  • CC chemokine receptor 9
  • Immunologic Factors
  • Integrin alpha Chains
  • Receptors, CCR
  • alpha E integrins
  • Integrin alpha4
  • Tretinoin