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

Runx/Cbfβ在肠道常规树突状细胞中启动Rorγt(+) T细胞的关键功能

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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.

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