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

ABSTRACT: 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 CD103⁺CD11b⁺ cDC2s and alters characteristics of CD103^-CD11b⁺ 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 Rorc 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.

SUBMITTER: Tenno M 

PROVIDER: S-EPMC6907387 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature