Signaling via the kinase p38? 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 here that the mitogen-activated protein kinase p38? programmed DCs to drive the differentiation of the T(H)17 subset of helper T cells. Deletion of p38? in DCs protected mice from T(H)17 cell-mediated autoimmune neuroinflammation, but deletion of p38? in macrophages or T cells did not. We also found that p38? orchestrated the expression of cytokines and costimulatory molecules in DCs and further 'imprinted' signaling via the receptor for interleukin 23 (IL-23R) in responding T cells to promote T(H)17 differentiation. Moreover, p38? was required for tissue-infiltrating DCs to sustain T(H)17 responses. This activity of p38? was conserved in mouse and human DCs and was dynamically regulated by pattern recognition and fungal infection. Our results identify p38? signaling as a central pathway for the integration of instructive signals in DCs for T(H)17 differentiation and inflammation.

SUBMITTER: Huang G 

PROVIDER: S-EPMC3262925 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature