| First Author | Konieczny P | Year | 2022 |
| Journal | Science | Volume | 377 |
| Issue | 6602 | Pages | eabg9302 |
| PubMed ID | 35709248 | Mgi Jnum | J:326739 |
| Mgi Id | MGI:7310510 | Doi | 10.1126/science.abg9302 |
| Citation | Konieczny P, et al. (2022) Interleukin-17 governs hypoxic adaptation of injured epithelium. Science :eabg9302 |
| abstractText | Mammalian cells autonomously activate hypoxia-inducible transcription factors to ensure survival in low-oxygen environments. We report that injury-induced hypoxia is insufficient to trigger hypoxia-inducible factor 1 alpha (HIF1alpha) in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that RORgammat(+) gammadelta T cell-derived interleukin (IL)-17A, is necessary and sufficient to activate HIF1alpha. Protein kinase B (AKT) and ERK1/2 signaling proximal of IL-17RC activates mammalian target of rapamycin (mTOR) and consequently HIF1alpha. The IL-17A-HIF1alpha drives glycolysis in wound front epithelia. Epithelial-specific loss of IL-17RC, HIF1alpha, or blockade of glycolysis derails repair. Our findings underscore the coupling of inflammatory, metabolic, and migratory programs to expedite epithelial healing and illuminate the immune cell-derived inputs in cellular adaptation to hypoxic stress during repair. |
