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- W4313366228 abstract "Abstract Mucosal CD103+ (αE integrin+) DCs are critically involved in driving a T regulatory response and enabling mucosal homeostasis. However, the regulation of CD103 expression in human DCs is not fully understood. We previously found that retinoic acid (RA) induces CD103 expression in human monocyte-derived DCs (MoDCs). Here, we investigated the molecular mechanisms leading to RA-induced CD103 expression on human DCs. We used a phospho-protein array to screen RA-treated MoDCs and found multiple potential targets. We focused on p38 MAPK based on previous studies that showed reduced CD103+ DCs in p38 MAPK KO mice. Western blots confirmed increased phosphorylation of p38 MAPK in RA-treated MoDCs. To determine whether p38 MAPK signaling influences CD103 expression, we next used an inhibitor of p38 MAPK and evaluated CD103 expression on MoDCs. The p38 MAPK inhibitor SB202190 significantly decreased expression of CD103 protein and mRNA in RA treated, but not in control MoDCs (p=0.037 and p=0.047 respectively). The transcription factor NFAT1c is a downstream target of p38 MAPK that has been shown to bind to the promotor region of CD103 in T cells. To determine whether NFAT1c regulates RA-induced CD103 expression, we next exposed RA-treated MoDCs to an NFAT1c peptide inhibitor. We demonstrated a significant dose-dependent decrease in CD103 protein expression of RA-treated MoDCs with increasing concentrations of the NFAT1c inhibitor (p=0.03). These data indicate that RA-induced expression of CD103 is dependent on p38 MAPK signaling and NFAT1c in human DCs and give insight into molecular mechanisms of DC signaling." @default.
- W4313366228 created "2023-01-06" @default.
- W4313366228 creator A5030865383 @default.
- W4313366228 creator A5048819862 @default.
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- W4313366228 date "2019-05-01" @default.
- W4313366228 modified "2023-09-27" @default.
- W4313366228 title "Retinoic acid-induced expression of CD103 in human DCs is dependent on p38 MAPK signaling and NFAT1c" @default.
- W4313366228 doi "https://doi.org/10.4049/jimmunol.202.supp.59.16" @default.
- W4313366228 hasPublicationYear "2019" @default.
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