Differential regulation of CD103 (alphaE integrin) expression in human dendritic cells by retinoic acid and Toll-like receptor ligands
Mandi M. Roe, Steve Swain, T Andrew Sebrell, Maris A. Sewell, Madison M. Collins, Brian A. Perrino, Phillip D. Smith, Lesley E. Smythies, Diane Bimczok
Journal of Leukocyte Biology
CD103 (alphaE integrin) is an important dendritic cell (DC) marker that characterizes functionally distinct DC subsets in mice and humans. However, the mechanism by which CD103 expression is regulated in human DCs and the role of CD103 for DC function are not very well understood. Here, we show that retinoic acid (RA) treatment of human monocyte-derived DCs (MoDCs) increased the ability of the DCs to synthesize RA and induced MoDC expression of CD103 and beta7 at the mRNA and protein level. In contrast, RA was unable to induce the expression of CD103 in primary human DCs isolated from the gastric mucosa. Inhibition of TGF-beta signaling in MoDCs down-regulated RA-induced CD103 expression, indicating that TGF-beta-dependent pathways contribute to the induction of CD103. Conversely, when RA-treated MoDCs were stimulated with live Helicobacter pylori, commensal bacteria, LPS, or a TLR2 agonist, the RA-induced up-regulation of CD103 and beta7 integrin expression was completely abrogated. To determine whether CD103 expression impacts DC priming of CD4+ T cells, we next investigated the ability of CD103+ and CD103? DCs to induce mucosal homing and T cell proliferation. Surprisingly, RA treatment of DCs enhanced both alpha4beta7 expression and proliferation in cocultured T cells, but no difference was seen between RA-treated CD103+ and CD103? DCs. In summary, our data demonstrate that RA, bacterial products, and the tissue environment all contribute to the regulation of CD103 on human DCs and that DC induction of mucosal homing in T cells is RA dependent but not CD103 dependent.
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