1. p38 MAPK signaling mediates retinoic acid‐induced CD103 expression in human dendritic cells
- Author
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Mandi Roe, Dianeiane Bimczok, Steve D. Swain, Marziah Hashimi, and Krista M. Woo
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cell type ,Small interfering RNA ,p38 mitogen-activated protein kinases ,Immunology ,Retinoic acid ,Tretinoin ,chemical and pharmacologic phenomena ,p38 Mitogen-Activated Protein Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Antigens, CD ,Humans ,Immunology and Allergy ,Gene silencing ,Phosphorylation ,RNA, Small Interfering ,Receptor ,Protein kinase A ,Cells, Cultured ,Retinoic Acid Receptor alpha ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Original Articles ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Integrin alpha Chains ,Signal Transduction ,030215 immunology - Abstract
Retinoic 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 α (E)), 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.
- Published
- 2020