SVα-MSH, a novel α-melanocyte stimulating hormone analog, ameliorates autoimmune encephalomyelitis through inhibiting autoreactive CD4+ T cells activation

•SVα-MSH, a novel α-MSH analog, acts as a novel immunotherapeutic approach for EAE.•SVα-MSH treatment induced Treg cells production and reduced Th17 cells in EAE mice.•SVα-MSH down-regulates T cell activation markers CD69 and CD134 on TPLP139–151 cells.•SVα-MSH did not induce apoptosis but blocked the G1/S phase transition.•SVα-MSH reduced cyclin E, Cdk2 expression and the activity of NFAT and AP-1.

Alpha-melanocyte stimulating hormone (α-MSH) plays a crucial role in the regulation of immune and inflammatory reactions. Here we report that SVα-MSH, a novel α-MSH analog, could ameliorate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in a preventive and therapeutic manner. SVα-MSH treatment induced the production of regulatory T (Treg) cells and reduced the Th17 cells in the CNS of EAE mice. SVα-MSH-treated PLP peptide 139–151-specific T cells showed a down-regulation of T cell activation markers CD69 and CD134. SVα-MSH did not induce apoptosis but blocked the G1/S phase transition, reduced the expression of cyclin E, Cdk2 and the activity of NFAT and AP-1 transcription factors. Thus, SVα-MSH acts as a novel immunotherapeutic approach in the treatment of autoimmune attack on the CNS.