917 Amphiregulin-producing innate lymphoid cells promote barrier response after mechanical damage

Epidermal hyperplasia is a protective response to restore disrupted skin barrier. Innate lymphoid cells (ILCs) have recently emerged as crucial resident immune for tissue homeostasis; however, how ILCs regulate the barrier after mechanical damage under physiological conditions remains unclear. In this study, we found that by mild tape stripping (T/S) induced epidermal with increased expression of proteins in WT mice and Rag2−/− (no T B cells), but was significantly reduced Rag2−/−Il2rg−/− ILCs). single cell RNAseq EdU pulse experiments, keratinocyte proliferation T/S mice, suggesting ILC promoted restoration via epithelial proliferation. While IL-7-deficient ILC2/3) responded similarly IL-15 deficient ILC1) showed hyperplasia. Unexpectedly, ILC1 major source Amphiregulin (AREG) both murine human skin, deficiency AREG led significant reduction Interestingly, release ATP from explants, highly sensitive sensor visualized extracellular (eATP) primary cultured keratinocytes stimulation. Furthermore, eATP receptor inhibitors suppressed T/S. Finally, performed Raman microscope imaging investigate damage-induced changes oxidative stress-related Increased anti-oxidant Rag2−/−mice less prominent lacking ILC1. Indeed, DNA epidermis more accumulated Taken together, ILC1-derived plays role eATP-induced protection stress.