Introduction: Macrophages vary in their functions, from pro-inflammatory to pro-reparative in guiding angiogenesis or producing growth factors to modulate stem cell activity. Our previous gene expression array has shown the dominant role of interleukin 17 (IL17) in the transition from inflammatory to repair macrophages in wounds. In the present study, we aimed to identify the function of IL17 in models of delayed wound healing and asked if its regulation was dependent on IL23.
Methods: We compared wounds from 8-15 week old mice deficient in IL-17 IL-23 and IL-12 subunits: P19 (IL23), P35 (IL12) and P40 (both IL12 and IL23) to wild type mice, all animals on a C57Bl/6 background. We also compared leptin deficient Ob/Ob mice to Ob/Ob IL17KO or to Ob/Ob mice treated with anti-IL17 antibodies.
Results: The accelerated wound healing in IL17KO mice were dependant on increased angiogenesis, however myofibroblast recruitment and differentiation, and epidermal closure were not significantly accelerated. Most importantly and expectedly, IL17KO mice had an increased proportion of non-inflammatory macrophages. In IL-17 deficient obese mice we observed a significant decrease in iNOS expression, a marker of inflammatory macrophages. P19 deficiency reproduced the increase in the proportion of non-inflammatory macrophages in the wound observed at D2 in IL17KO mice. There was a significant decrease in double positive IL17/F4:80 cells in all knockouts compared to WT. Using real-time PCR, we identified a significant decrease in IL17 and IL22 RNA expression in IL17KO, P19 KO and P40 KO mice compared to control suggesting that p35 (IL12) KO mice could still produce IL17. Finally, we also identified a significant increase of alpha-smooth muscle actin unique to P35KO mice compared to all other mice.
In conclusion, IL17 deficiency accelerates wound healing by reducing inflammation and improving angiogenesis. IL17 production in wounds seems to be dependent on IL23 but not IL12.