Microbiota upregulate distinct APC functions in each intestinal dendritic cell subset, in a Myd88-independent fashion

While dendritic cells (DCs) are known to control T cell responses to pathogens, how dynamics between DCs and microbiota impact mucosal T cells is poorly defined. To understand how microbiota impact APC functions of intestinal DCs, we use DCs lacking A20, a signaling attenuator, to amplify DC responses to microbiota. We find each intestinal DC subset possesses unique APC functions that enforces strict subset-specific rules to DC-instruction of either IFNg + or IL-17 + T cells. While CD103 + CD11b − DCs have potent abilities to instruct IFNg + T cells, these DCs do not induce IL-17 + T cells. In mirror image, CD103 + CD11b + DCs induce robust numbers of IL-17 + T cells, but induce no IFNg + T cells. By contrast, CD103 − CD11b + DCs possess dual abilities to instruct IFNg + and IL-17 + T cells. Interestingly, distinct mechanisms govern IFNg- and IL-17-inducing APC functions of intestinal DCs: While CD80/86 is required for DC-instruction of IFNg + T cells, DC-instruction of IL-17 + T cells requires IL-6. We further show that MyD88, although notorious in ability to upregulate APC functions, are not required to upregulate APC functions of intestinal CD103 + DCs. In support of this, we find that mice with DC specific loss of both A20 and MyD88 spontaneously develop inflammation of small intestine. Finally, we ablate CD103 − CD11b + DCs and CD103 + CD11b + DCs and find that these DCs are required for expansion of pathological Th17 cells. These results suggest that microbiota trigger distinct APC functions in different DC subsets and that in the context of intestinal inflammation and disease, there are defined teacher-student relationships between specific DC subsets and specific mucosal T cells.