STAT3 regulates innate immune response during tissue repair: a potential role for mitochondrial STAT3 3710

Abstract Description The Signal transducer and activator of transcription 3 (STAT3) is known to regulate innate immune cell activation and migration. We previously showed that STAT3 regulates wound healing. Since innate immunity plays an essential role in tissue repair, we examined the contribution of STAT3 in the innate immune response following caudal fin transection of larval zebrafish. Using both genetic depletion and pharmacologic inhibition of STAT3, combined with fluorescence microscopy of transgenic reporter lines, we found that STAT3 depletion impairs wound healing, macrophage and neutrophil recruitment, and alters macrophage spatial distribution at the wound. Interestingly, pharmacological inhibition of nuclear STAT3 activity impaired wound healing and macrophage recruitment; however, did not recapitulate the altered neutrophil recruitment and macrophage spatial distribution observed in the STAT3 mutant, suggesting that non-canonical STAT3 activity might be involved. Recent findings indicate that pSer727-STAT3 translocates to mitochondria (mitoSTAT3), exerting a non-canonical role in cellular metabolism. The role of mitoSTAT3 in immune cell function remains unexplored. We will continue to study mitoSTAT3 using genetic and pharmacological approaches. This study highlights the importance of STAT3 in innate immune cell-mediated inflammation and reveals a potential role for mitoSTAT3 in wound healing, offering insights into therapeutic strategies targeting STAT3 to improve tissue repair. Funding Sources NIH K99/R00GM138699 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)