| First Author | Feng T | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 10 | Pages | 5915-25 |
| PubMed ID | 20944006 | Mgi Jnum | J:165627 |
| Mgi Id | MGI:4837944 | Doi | 10.4049/jimmunol.1001233 |
| Citation | Feng T, et al. (2010) Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic Acid. J Immunol 185(10):5915-25 |
| abstractText | 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-beta 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-beta production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity. |
