| First Author | Liu S | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 10 | Pages | 2127-2143.e22 |
| PubMed ID | 37098344 | Mgi Jnum | J:340999 |
| Mgi Id | MGI:7483973 | Doi | 10.1016/j.cell.2023.03.031 |
| Citation | Liu S, et al. (2023) A tissue injury sensing and repair pathway distinct from host pathogen defense. Cell 186(10):2127-2143.e22 |
| abstractText | Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections and induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast to most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after tissue injury and is independent of microbiome or adaptive immunity. Moreover, Il24 ablation in mice impedes not only epidermal proliferation and re-epithelialization but also capillary and fibroblast regeneration within the dermal wound bed. Conversely, ectopic IL-24 induction in the homeostatic epidermis triggers global epithelial-mesenchymal tissue repair responses. Mechanistically, Il24 expression depends upon both epithelial IL24-receptor/STAT3 signaling and hypoxia-stabilized HIF1alpha, which converge following injury to trigger autocrine and paracrine signaling involving IL-24-mediated receptor signaling and metabolic regulation. Thus, parallel to innate immune sensing of pathogens to resolve infections, epithelial stem cells sense injury signals to orchestrate IL-24-mediated tissue repair. |
