Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct...

Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103⁺CD11b^- DCs exclusively instruct IFNγ⁺ T cells, CD103⁺CD11b⁺ DCs exclusively instruct IL-17⁺ T cells. Surprisingly, APC functions of both DC subsets are upregulated in a MyD88-independent fashion. In contrast, CD103^-CD11b⁺ DCs instruct both IFNγ⁺ and IL-17⁺ T cells, and only the IL-17-inducing APC functions require MyD88. In disease pathogenesis, both CD103^-CD11b⁺ and CD103⁺CD11b⁺ DCs expand pathologic Th17 cells. Thus, in disease pathogenesis, specific DCs instruct specific inflammatory T cells.