A tissue injury sensing and repair pathway distinct from host pathogen defense.
| Publication Type | Academic Article |
| Authors | Liu S, Hur Y, Cai X, Cong Q, Yang Y, Xu C, Bilate A, Gonzales K, Parigi S, Cowley C, Hurwitz B, Luo J, Tseng T, Gur-Cohen S, Sribour M, Omelchenko T, Levorse J, Pasolli H, Thompson C, Mucida D, Fuchs E |
| Journal | Cell |
| Volume | 186 |
| Issue | 10 |
| Pagination | 2127-2143.e22 |
| Date Published | 04/24/2023 |
| ISSN | 1097-4172 |
| Keywords | Cytokines, Wounds and Injuries |
| Abstract | 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 HIF1α, 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. |
| DOI | 10.1016/j.cell.2023.03.031 |
| PubMed ID | 37098344 |
| PubMed Central ID | PMC10321318 |