Essential functions of Runx/Cbfβ in gut conventional dendritic cells for priming Rorγt T cells.

Acquired immune responses are initiated by activation of CD4 helper T (Th) cells via recognition of antigens presented by conventional dendritic cells (cDCs). DCs instruct Th-cell polarization program into specific effector Th subset, which will dictate the type of immune responses. Hence, it is important to unravel how differentiation and/or activation of DC are linked with Th-cell-intrinsic mechanism that directs differentiation toward a specific effector Th subset. Here, we show that loss of Runx/Cbfβ transcription factors complexes during DC development leads to loss of CD103CD11b cDC2s and alters characteristics of CD103CD11b cDCs in the intestine, which was accompanied with impaired differentiation of Rorγt Th17 cells and type 3 Rorγt regulatory T cells. We also show that a Runx-binding enhancer in the gene is essential for T cells to integrate cDC-derived signals to induce Rorγt expression. These findings reveal that Runx/Cbfβ complexes play crucial and complementary roles in cDCs and Th cells to shape converging type 3 immune responses.