NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence

Abstract During skin injury, immune response and repair mechanisms have to be coordinated for rapid regeneration the prevention of microbial infections. Natural Killer (NK) cells infiltrate hypoxic lesions Hypoxia-inducible transcription factors (HIFs) mediate adaptation low oxygen. We demonstrate that mice lacking factor (HIF)-1α isoform in NK show impaired release cytokines Interferon (IFN)-γ Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) as part a blunted response. This accelerates angiogenesis wound healing. Despite closure, bactericidal activity ability restrict systemic bacterial infection are impaired. Conversely, forced activation HIF pathway supports cytokine cell-mediated antibacterial defence including direct killing bacteria by despite delayed closure. Our results identify, HIF-1α nexus balances antimicrobial versus global skin.