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The pathogenesis of keloids has not been elucidated, and the disease is thought to be caused by abnormal secretion of proinflammatory mediators and irregular responses to other inflammatory signals mediated by keloid fibroblasts (KFs). In this study, we investigated whether a local increase in interleukin IL-17 in keloid tissues stimulates the production of stromal cell–derived factor-1 (SDF-1) in KFs causing further recruitment of IL-17-producing T helper 17 (Th17) cells, which subsequently creates a positive feedback loop. Histological assessment was performed and the change in the expression of IL-17, IL-1β, IL-6, and TNF-α which of fibrosis and inflammation associated markers was examined. In addition, fibroblasts were treated with IL-17 in the presence or absence of STAT3 inhibitor STA-21; SDF-1 levels and fibrosis genes were measured. Our results showed that fibrotic reaction and expression of proinflammatory cytokines including IL-17 were most prominent in the growing margin (perilesional area) of keloid tissue and Th17 cells significantly infiltrated the perilesional area. In addition, IL-17 upregulated the expression of SDF-1, collagen, and α-SMA in KFs. Finally, STA-21 decreased SDF-1α expression and the expression of fibrosis genes in KFs even after IL-17 stimulation. Our study demonstrated that a local increase in IL-17 in keloid tissues stimulates the production of SDF-1 in KFs causing further recruitment of IL-17-producing T helper 17 (Th17) cells, which subsequently creates a positive feedback loop. These findings suggest that STAT3 inhibition can be used to treat keloid scars by reversing the vicious cycle between Th17 cells and KFs.

IL-17 Induced Stromal Cell–Derived Factor-1 and Profibrotic Factor in Keloid-Derived Skin Fibroblasts via the STAT3 Pathway