The microRNA-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids

MicroRNA-126 (miR-126) is a microRNA predominately expressed by endothelial cells and controls angiogenesis. We found miR-126 was required for the innate response to pathogen-associated nucleic acids, and that miR-126-deficient mice had increased susceptibility to pseudotyped-HIV infection. miRNA profiling and deep-sequencing indicated that miR-126 was highly and specifically expressed by plasmacytoid dendritic cells (pDCs). miR-126 controlled the survival and function of pDCs, and regulated expression ofinnate response genes, including Tlr7, Tlr9 and Nfkb1, as well as Kdr, which encodes VEGF-receptor 2 (VEGFR2). Deletion of Kdr in DCs resulted in reduced type I interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126–VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.