| Autor: |
McDonald, Keely G., Leach, Matthew R., Brooke, Kaitlin W.M., Wang, Caihong, Wheeler, Leroy W., Hanly, Elyse K., Rowley, Christopher W., Levin, Marc S., Wagner, Michael, Li, Ellen, Newberry, Rodney D. |
| Zdroj: |
American Journal of Pathology; March 2012, Vol. 180 Issue: 3 p984-997, 14p |
| Abstrakt: |
Dendritic cells (DCs) use all-trans retinoic acid (ATRA) to promote characteristic intestinal responses, including Foxp3+Treg conversion, lymphocyte gut homing molecule expression, and IgA production. How this ability to generate ATRA is conferred to DCs in vivoremains largely unstudied. Here, we observed that among DCs, retinaldehyde dehydrogenase (ALDH1), which catalyzes the conversion of retinal to ATRA, was preferentially expressed by small intestine CD103+lamina propria (LP) DCs. Retinoids induced LP CD103+DCs to generate ATRA via ALDH1 activity. Either biliary or dietary retinoids were required to confer ALDH activity to LP DCs in vivo. Cellular retinol-binding protein II (CRBPII), a cytosolic retinoid chaperone that directs enterocyte retinol and retinal metabolism but is redundant to maintain serum retinol, was required to confer ALDH activity to CD103+LP DCs. CRBPII expression was restricted to small intestine epithelial cells, and ALDH activity in CRBPII−/−DCs was restored by transfer to a wild-type recipient. CD103+LP DCs from CRBPII−/−mice had a decreased capacity to promote IgA production. Moreover, CD103+DCs preferentially associated with the small intestine epithelium and LP CD103+DC ALDH activity, and the ability to promote IgA production was reduced in mice with impaired DC–epithelia associations. These findings demonstrate in vivoroles for the expression of epithelial CRBPII and lumenal retinoids to imprint local gut DCs with an intestinal phenotype. |
| Databáze: |
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