| First Author | Huang G | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 2 | Pages | 152-61 |
| PubMed ID | 22231518 | Mgi Jnum | J:181211 |
| Mgi Id | MGI:5309076 | Doi | 10.1038/ni.2207 |
| Citation | Huang G, et al. (2012) Signaling via the kinase p38alpha programs dendritic cells to drive TH17 differentiation and autoimmune inflammation. Nat Immunol 13(2):152-61 |
| abstractText | 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 p38alpha programmed DCs to drive the differentiation of the T(H)17 subset of helper T cells. Deletion of p38alpha in DCs protected mice from T(H)17 cell-mediated autoimmune neuroinflammation, but deletion of p38alpha in macrophages or T cells did not. We also found that p38alpha 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, p38alpha was required for tissue-infiltrating DCs to sustain T(H)17 responses. This activity of p38alpha was conserved in mouse and human DCs and was dynamically regulated by pattern recognition and fungal infection. Our results identify p38alpha signaling as a central pathway for the integration of instructive signals in DCs for T(H)17 differentiation and inflammation. |
