A tissue injury sensing and repair pathway distinct from host pathogen defense Journal Article
| Authors: | Liu, S.; Hur, Y. H.; Cai, X.; Cong, Q.; Yang, Y.; Xu, C.; Bilate, A. M.; Gonzales, K. A. U.; Parigi, S. M.; Cowley, C. J.; Hurwitz, B.; Luo, J. D.; Tseng, T.; Gur-Cohen, S.; Sribour, M.; Omelchenko, T.; Levorse, J.; Pasolli, H. A.; Thompson, C. B.; Mucida, D.; Fuchs, E. |
| Article Title: | A tissue injury sensing and repair pathway distinct from host pathogen defense |
| 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. © 2023 The Authors |
| Keywords: | mouse; animal; animals; mice; epidermis; angiogenesis; hypoxia; cytokine; cytokines; chemokine; innate immunity; immunity, innate; adaptive immunity; tissue injury; chemokines; stat3; innate immune signaling; interferons; coordinated tissue repair; epithelial stem cells; interleukin-24; microbiome-independent responses |
| Journal Title: | Cell |
| Volume: | 186 |
| Issue: | 10 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2023-05-11 |
| Start Page: | 2127 |
| End Page: | 2143.e22 |
| Language: | English |
| DOI: | 10.1016/j.cell.2023.03.031 |
| PUBMED: | 37098344 |
| PROVIDER: | scopus |
| PMCID: | PMC10321318 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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