Signaling via the kinase p38α programs dendritic cells to drive TH17 differentiation and autoimmune inflammation

Abstract

Dendritic cells (DCs) bridge innate and adaptive immunity, but how DC-derived signals regulate T cell lineage choices remains unclear. We report that p38α MAP kinase programs DCs to drive TH17 differentiation. Deletion of p38α in DCs, but not macrophages or T cells, protects mice from TH17-mediated autoimmune neuroinflammation. p38α orchestrates expression of cytokines and co-stimulatory molecules in DCs, and further imprints T cell IL-23R signaling to promote TH17 differentiation. Moreover, p38α is required for tissue-infiltrating DCs to sustain TH17 responses. This activity of p38α is conserved between mouse and human DCs, and is dynamically regulated by pattern recognition and fungal infection. Our results identify p38α as a central pathway to integrate instructive signals in DCs for TH17 differentiation and inflammation.