Roe, Mandi M.Hashimi, MarziahSwain, SteveWoo, Krista M.Bimczok, Diane2022-03-022022-03-022020-11Roe, Mandi M., Marziah Hashimi, Steve Swain, Krista M. Woo, and Diane Bimczok. “P38 MAPK Signaling Mediates Retinoic Acid‐induced CD103 Expression in Human Dendritic Cells.” Immunology 161, no. 3 (September 14, 2020): 230–244. doi:10.1111/imm.13246.1365-2567https://scholarworks.montana.edu/handle/1/16674Retinoic acid (RA) is an active derivative of vitamin A and a key regulator of immune cell function. In dendritic cells (DCs), RA drives the expression of CD103 (integrin αE), a functionally relevant DC subset marker. In this study, we analyzed the cell type specificity and the molecular mechanisms involved in RA-induced CD103 expression. We show that RA treatment caused a significant up-regulation of CD103 in differentiated monocyte-derived DCs and blood DCs, but not in differentiated monocyte-derived macrophages or T cells. DC treatment with an RA receptor α (RARα) agonist led to an increase in CD103 expression similar to that in RA treatment, whereas RARA gene silencing with small interfering RNA blocked RA-induced up-regulation of CD103, pointing to a major role of RARα in the regulation of CD103 expression. To elucidate RA-induced signaling downstream of RARα, we used Western blot analysis of RA-treated DCs and showed a significant increase of p38 mitogen-activated protein kinase (MAPK) phosphorylation. In addition, DCs cultured with RA and a p38 MAPK inhibitor had a significantly reduced expression of CD103 compared with DCs cultured with RA only, indicating that p38 MAPK is involved in CD103 regulation. In summary, these findings suggest that the RA-induced expression of CD103 is specific to DCs, is mediated primarily through RARα and involves p38 MAPK signaling.en-USArticle