Decreased , , , and Transcripts Lead to Reduced Regulatory T Cells Suppressive Capacity in Generalized Vitiligo Patients

Generalized vitiligo (GV) is an autoimmune skin disease characterized by bilateral white patches over the entire body. Regulatory T cells (Tregs) maintain peripheral tolerance; however, they are found to be reduced in numbers and function in vitiligo patients. The exact mechanism for reduced Treg suppressive capacity is unknown. Therefore, we aimed to assess transcript levels of Tregs-associated immunosuppressive genes (, , , , and ), regulatory molecules of Tregs suppressive function (, , and ), and Treg-associated transcription factors (, , , , and ) in 52 GV patients and 48 controls by real-time PCR (qPCR). We found significantly reduced , , , and transcripts in GV Tregs compared to controls ( = 0.03, = 0.023, = 0.0045, and < 0.0001, respectively). There were 0.44-, 0.45-, 0.32-, and 0.54-fold decrease in , , , and transcripts in GV Tregs. Additionally, disease activity and severity-based analyses revealed significantly decreased ( = 0.019 and 0.034), ( = 0.031 and = 0.035), and ( = 0.0003 and = 0.034) transcripts in active vitiligo and severe GV patients' Tregs. Interestingly, we found a positive correlation for with ( = 0.45, = 0.0009) and ( = 0.52, = 0.001) transcripts in GV Tregs. Moreover, we found positive correlation for percentage Treg mediated suppression of CD4 and CD8T cells with ( = 0.54; = 0.49), ( = 0.61; = 0.58), ( = 0.55; = 0.52), and ( = 0.56; = 0.48) in GV Tregs. Further, calcium treatment of Tregs resulted into significantly increased , , and transcripts in GV Tregs ( = 0.023, = 0.0345, = 0.02). Overall, our results for the first time revealed the crucial role of , , , and transcripts in decreased Treg suppressive capacity leading to GV pathogenesis, progression, and severity. In addition, our study highlighted that might be linked with decreased and expression in GV Tregs. Moreover, our study for the first time suggest that increased transcripts may lead to endogenous granzyme B-mediated Tregs apoptosis, and calcium treatment of Tregs may improve the Treg suppressive capacity. These findings may further aid in development of Treg-based therapeutics for GV.