Langerhans cells are essential components of the angiogenic niche during murine skin repair

Angiogenesis, the growth of new blood vessels from pre-existing vessels, occurs during development, injury repair, and tumorigenesis to deliver oxygen, immune cells, and nutrients to tissues. Defects in angiogenesis occur in cardiovascular and inflammatory diseases, and chronic, non-healing wounds, yet treatment options are limited. Here, we provide a map of the early angiogenic niche by analyzing single-cell RNA sequencing of mouse skin wound healing. Our data implicate Langerhans cells (LCs), phagocytic, skin-resident immune cells, in driving angiogenesis during skin repair. Using lineage-driven reportersw, three-dimensional (3D) microscopy, and mouse genetics, we show that LCs are situated at the endothelial cell leading edge in mouse skin wounds and are necessary for angiogenesis during repair. These data provide additional future avenues for the control of angiogenesis to treat disease and chronic wounds and extend the function of LCs beyond their canonical role in antigen presentation and T cell immunity. [Display omitted] •scRNA sequencing provides a map of the angiogenic niche during skin repair•Langerhans cells upregulate angiogenic mRNAs after injury•Langerhans cells localize to angiogenic blood vessel tips in wound beds•Langerhans cells are necessary for proper angiogenesis and repair after injury in mice Angiogenesis repairs blood vessels after injury by creating new blood vessels from pre-existing endothelial cell networks. Using scRNA sequencing, Wasko et al. provide a map of the predicted molecular and cellular cues that drive angiogenesis and identify Langerhans cells as a major regulator of angiogenesis in murine skin wounds.