Cell-extrinsic effects of Irf2 on cDC2 development

Abstract

Characterization of the functional effects of cDC2s in vivo requires model systems in which cDC2s are depleted. Previous literature has reported a loss of cDC2s in mice lacking the transcription factor IRF21,2. We sought to further characterize the cDC2 defect in these animals. Here, we find that the requirement for IRF2 in cDC2 development and survival is cell-extrinsic and correlated to the development of dermatitis in the Irf2-/- model system. We also find that Flt3L-mediated in vitro development of cDC1s and cDC2s, but not pDCs, is abrogated in Irf2-/- bone marrow, as well as in wild-type bone marrow cultured with IFN. Loss of interferon (IFN) signaling in Irf2-/- mice restored cDC2 development in vivo and cDC1 and cDC2 development in vitro. We therefore conclude that IRF2 is required for cDC2 development in a cell-extrinsic manner dependent on IFN signaling.