Presence and the roles of IL-9/Th9 axis in vitiligo

Immune dysregulation is critical in vitiligo pathogenesis. Although the presence and roles of numerous CD4⁺ T-cell subsets have been described, the presence of Th9 cells and more importantly, roles of IL-9 on melanocyte functions are not explored yet. Here, we quantified the T helper cell subsets including Th9 cells in vitiligo patients by multicolor flowcytometry. There was an increased frequency of skin-homing (CLA⁺ ) and systemic (CLA^- ) Th9 cells in vitiligo patients compared to healthy donors. However, there was no difference in Th9 cell frequency in vitiligo patients with early and chronic disease. There was negligible IL-9 receptor (IL-9R) expression on human primary melanocytes (HPMs); however, IFNγ upregulated IL-9R expression on HPMs. Functionally, IL-9/IL-9R signaling reduced the production of IFNγ-induced toxic reactive oxygen species (ROS) in HPMs. There was no effect of IL-9 on expression of genes responsible for melanosome formation (MART1, TYRP1, and DCT), melanin synthesis (TYR), and melanocyte-inducing transcription factor (MITF) in HPMs. In conclusion, this study identifies the presence of Th9 cells in vitiligo and their roles in reducing the oxidative stress of melanocytes, which might be useful in designing effective therapeutics.