Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid

Ting Feng, Yingzi Cong, Hongwei Qin, Etty N. Benveniste, Charles O. Elson

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.

Original languageEnglish (US)
Pages (from-to)5915-5925
Number of pages11
JournalJournal of Immunology
Volume185
Issue number10
DOIs
StatePublished - Nov 15 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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