CCL6 promotes M2 polarization and inhibits macrophage autophagy by activating PI3-kinase/Akt signaling pathway during skin wound healing.

The transition of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype is crucial during the wound healing process. In this study, we assess the role of chemokine (C-C motif) ligand 6 (CCL6) in modulating macrophage polarization and wound healing. Initially, we observed significantly upregulated CCL6 expression in the skin tissue on the edge of the wound during the inflammation and proliferation phases. Furthermore, we discovered that the mice treated with rCCL6 had significantly accelerated wound healing and increased levels of M2-type macrophages. Using in vitro models, we found that CCL6 promotes the M2 polarization of macrophages by activating the PI3-kinase/Akt signaling pathway. Additionally, our results showed that CCL6 inhibited macrophage autophagy and accelerated wound healing, whereas the autophagy inducer rapamycin delayed wound healing. Finally, we determined that the PI3-kinase inhibitor LY294002 promoted macrophage autophagy and decreased M2 macrophages, indicating the importance of PI3-K in M2 polarization, and this process was reversed by CCL6. Taken together, our study demonstrates that CCL6 promotes M2 polarization, inhibits macrophage autophagy, and accelerates skin wound healing by activating the PI3-kinase/Akt signaling pathway.