A tissue injury sensing and repair pathway distinct from host pathogen defense.
Cell
; 186(10): 2127-2143.e22, 2023 05 11.
Article
in En
| MEDLINE
| ID: mdl-37098344
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Wounds and Injuries
/
Cytokines
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2023
Type:
Article
Affiliation country:
United States