Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88

Abstract

Summary: 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. : Normal dynamics between microbiota and dendritic cells (DCs) support T cell homeostasis in the small intestine, but the dynamics that drive inflammation are not clear. Liang et al. show that distinct subsets of dendritic cells drive pathogenic Th1 versus Th17 differentiation. Keywords: dendritic cells, small intestine, Th1, Th17, inflammation, MyD88, A20