Model depicting the similarities between evolutionarily conserved pathogen-induced IFN signaling for defense and injury-induced IL-24 signaling for repair. In contrast to pathogens, which lead to induction of IFN and p-STAT1/2, tissue damage causes hypoxia, leading to HIF1α, IL-24, and p-STAT3. Specifically, EpdSCs sense wound hypoxia caused by severed blood vessels, and induce IL-24 and receptor signaling, which subsequently activates STAT3 and further fuelsIl24expression to promote a coordinated dermal repair and re-epithelialization. The autocrine and paracrine mechanisms underlying wound-induced IL-24-signaling in tissue repair are parallel and functionally analogous to pathogen-induced IFN signaling in pathogen defense, and the two pathways share multiple levels of homology. White dotted lines, epidermal-dermal border; wound site, red dotted line; epidermal migration direction, red arrow. DAPI, nuclei; scale bars, 100 μm. Data in (A) and (C)–(F) are presented as mean ± SEM. Experiments were performed ≥ 3×. Statistical significance was determined using two-way ANOVA and Tukey’s multiple comparisons tests in (A) and (E), using one-way ANOVA and Tukey’s multiple comparisons tests in figure (C), and using two-tailed unpaired Student’s t tests in (F);****p < 0.0001;***p < 0.001;**p < 0.01;*p < 0.05; and ns, not significant.
