Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

We report that like HSPCs, cDCs express Etv6, but not its antagonist, ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors. Deletion of Etv6 in the bone marrow impaired the generation of cDC1-like cells in vitro and abolished the expression of signature marker CD8α on cDC1 in vivo. Moreover, Etv6-deficient primary cDC1 showed a partial reduction of cDC-specific and cDC1-specific gene expression and chromatin signatures and an aberrant up-regulation of pDC-specific signatures. Accordingly, DC-specific Etv6 deletion impaired CD8+ T cell cross-priming and the generation of tumor antigen–specific CD8+ T cells. Thus, Etv6 optimizes the resolution of cDC1 and pDC expression programs and the functional fitness of cDC1, thereby facilitating T cell cross-priming and tumor-specific responses.

Source: The Journal of Experimental Medicine - September 3, 2018 Category: Internal Medicine Authors: Lau, C. M., Tiniakou, I., Perez, O. A., Kirkling, M. E., Yap, G. S., Hock, H., Reizis, B. Tags: Innate Immunity and Inflammation, Tumor Immunology Brief Definitive Reports Source Type: research