To study the effect of lenalidomide on the melanocytes and cytotoxic cd8plus t lymphocytes in vitiligo mouse model and its therapeutic implications

Abstract

Vitiligo is a depigmentary disorder in which epidermal melanocytes are lost. Immunopathology of this disease includes altered levels of various cytokines and T lymphocytes. Lenalidomide is an immunomodulatory drug which alters cytokine production and regulates T cell stimulation. As there are no studies which have reported its effect on vitiligo, the present study, was designed to check the effect of lenalidomide on cultured human melanocytes, peripheral blood mononuclear cells (PBMCs) from vitiligo patients and development of lesions in vitiligo mouse model. It was observed that lenalidomide elevated the proliferation and migration of melanocytes and also enhanced the process of melanogenesis. Lenalidomide decreased the levels of pro-inflammatory cytokines (IFN-and#947; and TNF-and#945;), elevated the levels of anti-inflammatory cytokines (IL-4 and IL-10) and also raised CD4+ /CD8+ T cell ratio in the supernatant of cultured PBMCs. For in vivo studies, a vitiligo mouse model was developed and the effect of lenalidomide was observed on the development of vitiligo lesions, levels of T lymphocytes and various cytokines. In the mice models, it significantly inhibited the progression of vitiligo lesions by suppressing the serum level of pro-inflammatory cytokines (IFN-and#947;, TNF-and#945;, IL-1and#946; and IL-6) and increasing level of anti-inflammatory cytokines (IL-4 and IL-10). CD4+ /CD8+ T cell ratio was also elevated in blood of vitiligo mice models after lenalidomide treatment. Overall results of the study suggest possible therapeutic use of lenalidomide in the management of vitiligo, as it modulated the immune response towards an anti-inflammatory profile. newline