| First Author | Huang G | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 650-9 |
| PubMed ID | 23752611 | Mgi Jnum | J:204825 |
| Mgi Id | MGI:5543530 | Doi | 10.4049/jimmunol.1300398 |
| Citation | Huang G, et al. (2013) Control of T cell fates and immune tolerance by p38alpha signaling in mucosal CD103+ dendritic cells. J Immunol 191(2):650-9 |
| abstractText | Dendritic cells (DCs) play a crucial role in launching protective adaptive immunity against pathogens while maintaining immune tolerance to self-Ags. However, how intracellular signaling pathways program DCs to mediate tolerogenic responses remains largely unexplored. In this study, we describe that p38alpha signaling in CD103(+) mesenteric lymph node DCs reciprocally regulates the differentiation of anti-inflammatory induced regulatory T cells and proinflammatory Th1 cells from naive precursors and promotes mucosal tolerance. Deficiency of p38alpha in CD103(+) DCs inhibited the generation of induced regulatory T cells while promoting Th1 cell development in a TGF-beta2-dependent manner. Consequently, loss of p38alpha in DCs prevented induction of oral tolerance in vivo. Moreover, p38alpha in CD103(+) DCs was required for optimal expression of retinaldehyde dehydrogenase, a key enzyme for retinoic acid synthesis, which in turn imprinted gut-homing receptors on responding T cells. Consistent with a crucial role of p38alpha to program the tolerogenic activity of CD103(+) DCs, such DC subset contained constitutive activity of p38alpha and abundant expression of TGF-beta2 and retinaldehyde dehydrogenase. Our studies identify a key mechanism of DC-mediated coupling of T cell differentiation and trafficking that orchestrates mucosal immune tolerance. |
