Welc, Steven S.Wehling-Henricks, MichelleAntoun, JacquelineHa, Tracey T.Tous, IsabellaTidball, James G.2023-03-132023-03-132020-09-15Welc SS, Wehling-Henricks M, Antoun J, Ha TT, Tous I, Tidball JG. Differential Effects of Myeloid Cell PPARδ and IL-10 in Regulating Macrophage Recruitment, Phenotype, and Regeneration following Acute Muscle Injury. J Immunol. 2020;205(6):1664-1677. doi:10.4049/jimmunol.2000247https://hdl.handle.net/1805/31849Changes in macrophage phenotype in injured muscle profoundly influence regeneration. In particular, the shift of macrophages from a pro-inflammatory (M1-biased) phenotype to a pro-regenerative (M2-biased) phenotype characterized by expression of CD206 and CD163 is essential for normal repair. According to the current canonical mechanism regulating for M1/M2 phenotype transition, signaling through PPARδ is necessary for obtaining the M2-biased phenotype. Our findings confirm that the murine myeloid cell targeted deletion of Ppard reduces expression in vitro of genes that are activated in M2-biased macrophages; however, the mutation in mice in vivo increased numbers of CD206+ M2-biased macrophages and did not reduce the expression of phenotypic markers of M2-biased macrophages in regenerating muscle. Nevertheless, the mutation impaired CCL2-mediated chemotaxis of macrophages and slowed revascularization of injured muscle. In contrast, null mutation of IL10 diminished M2-biased macrophages but produced no defects in muscle revascularization. Our results provide two significant findings. First, they illustrate that mechanisms that regulate macrophage phenotype transitions in vitro are not always predictive of mechanisms that are most important in vivo. Second, they show that mechanisms that regulate macrophage phenotype transitions differ in different in vivo environments.en-USPublisher PolicySkeletal muscleInflammationAcute muscle injuryMacrophagePPARδInterleukin-10Article