Females Display Greater Disease Severity in a Mouse Model of Vitiligo
Kaitlyn G. O'Donnell, Zhussipbek Mukhatayev, Hanin Abuzer, Rohan S. Shivde, Sriram Saravanan Shanmugavelandy, Octavio K. Bartos, Ellis Kang, Emilia R. Dellacecca, Dinesh Jaishankar, Surya Pandey, Hee Kap Kang, Ziyou Ren, I. Caroline Le PooleABSTRACT
Vitiligo is an autoimmune disease characterized by progressive depigmentation of the skin due to T cell‐mediated destruction of melanocytes. Disease onset varies but usually initiates during adolescence. Sex differences in disease development and therapeutic outcomes have not been explored. We previously associated stress induced HSP70i with immune activation in depigmentation and showed that HSP70i Q435A can tolerize dendritic cells (DCs) to prevent cutaneous recruitment and activation of T cells. Among male and female vitiligo‐prone mice, we investigated the long‐term efficacy of HSP70i Q435A plasmid DNA treatment introduced by biolistic administration at varying stages of vitiligo development. Mice were followed up to 46 weeks of age. Female mice exhibited 1.89‐fold greater depigmentation than males overall, while both responded proportionally to treatment with effects lasting throughout. This sex difference was associated with significantly elevated IFN‐γ secretion by melanocyte‐reactive T cells among female mice. Humoral responses to the protein remained readily detectable at end point regardless of treatment interval. These findings also suggest greater benefit from earlier intervention.