Hair follicle stem cells repair wounds by converting effector T cells into regulatory T cells to shield against inflammation 2517

Description Hair follicle stem cells (HFSCs), located in the basal layer of skin epithelium, are crucial for maintaining and regenerating the surface barrier after injury. To perform these critical functions, these HFSCs are generally considered to reside within an immune privileged niche during homeostatic conditions. However, during wound repair, the mechanisms by which HFSCs protect themselves from the harsh inflammatory environment remain unclear since these HFSCs must be mobilized to migrate out of their original niche. Employing lineage tracing, RNA sequencing, and microscope imaging to track the wound-activated, migrating HFSCs during the wound healing, we found that these cells acquired CD80, an immunomodulatory ligand thought to be restricted to antigen-presentation cells. Ablation of CD80 specifically in HFSCs resulted in a significant impairment of wound healing. Mechanistic analysis revealed that CD80 in HFSCs orchestrates Treg cell responses to drive re-epithelization. Notably, we found that the expansion of Treg cells induced by CD80-expressing HFSCs is neither a result of increased differentiation from naïve CD4 T cells, nor induced by increased proliferation. Unexpectedly, co-culture assays showed that CD80+ HFSCs induced Foxp3 expression in sorted effector T cells, converting them into Treg cells. These finding suggested that CD80 presented by wound-activated HFSCs induces Foxp3 expression in effector T cells to build a protective barrier to enable wound repair. Funding Sources NIH R01CA285786 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)