Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis

Significance Dendritic cells (DCs) are known to mediate immune regulatory networks in response to intestinal epithelial barrier disruption, but underlying signaling pathways and molecular mechanisms are not well understood. Here, we show that genetic disruption of p38α in DCs leads to higher levels of differentiated type 1 regulatory T cells and group 3 innate lymphoid cells. Specifically, p38α signaling in intestinal cDC1s, but not cDC2s or T cells, mediates colitis pathogenesis. Together, our results suggest that p38α MAPK represents a major signaling network in DCs that regulates inflammation and contributes to epithelial barrier function in colitis and associated colorectal cancer. Furthermore, our finding suggests that p38α signaling in DCs may represent a target for the treatment of inflammatory intestinal diseases.