Expression of Th17- and Treg-specific transcription factors in vitiligo patients.

Abstract

Vitiligo is mainly considered an autoimmune skin disease as the number of IL-17 producing Th17 cells, involved in the development of autoimmune and inflammatory pathologies, increased in vitiligo skin. T regulatory cells (Tregs) seem to be altered during the disease. Thus, there must be some upstream molecular factors that regulate the cellular response to apoptotic and inflammatory stimuli. To investigate the expression of Th17- and Treg-specific transcription factors in PBMCs and to evaluate the correlation between these transcription factors and cytokines in vitiligo patients. We investigated 30 active NSV patients for Th17- and Treg-specific transcription factors RORγt (retinoic acid-related orphan receptor gamma t), FOXP3 (forkhead/winged helix), HELIOS, EOS, and IRF4 (Interferon Regulatory Factor 4) as well as apoptotic marker NALP1 (NACHT-leucine-rich-repeat protein 1) in PBMCs with RT-qPCR. Immunostaining was done for transcription factors and cytokines on skin sections. The mRNA level of FOXP3 was significantly lower in patients (0.76 fold, P<0.001), whereas RORγt was slight but notsignificantly increased (0.76 fold, P=0.06). Furthermore, NALP1 in lymphocytes was found to be increased in patients (0.69 fold, P<0.01). The immunostaining results revealed increased expression of RORγ, IL-17A, NALP1, and IL-1β in vitiligo skin when compared to normal healthy skin. Reduced FOXP3/RORγt mRNA ratio suggests thriving of the Th17 cell population in PBMCs of vitiligo patients. Increased NALP1 levels indicate the existence of an apoptotic phenomenon which correlates with the increased expression of IL-1β in vitiligo pathogenesis.