Retroviruses including Human Endogenous Retroviruses (HERVs), contain a conserved region with highly immunomodulatory functions in the transmembrane proteins in envelope gene (env) named immunosuppressive domain (ISU).

In this report, we demonstrate that Env59-GP3 peptide holds therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The results show that this specific HERV-H derived ISU peptide, but not peptide derived from another env gene HERV-K, decreased the development of EAE in C57BL/6 mice, accompanied by reduced demyelination and inhibition of inflammatory cells. Moreover, here we tested the effect of peptides on macrophages differentiation. The treatment with Env59-GPS peptide modulate the pro-inflammatory M1 profile and anti-inflammatory M2 macrophages, being shown by inhibiting inflammatory M1 hallmark genes/cytokines expression and enhancing expression of M2 associated markers. These results demonstrate that Env59-GP3 ISU peptide has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.

包括人类内源性逆转录病毒（HERV）在内的逆转录病毒在被称为免疫抑制域（ISU）的包膜基因（env）的跨膜蛋白中包含一个具有高度免疫调节功能的保守区域。

在此报告中，我们证明Env59-GP3肽在髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）的小鼠模型中具有治疗潜力。结果表明，这种特定的HERV-H衍生的ISU肽，而不是另一种env衍生的肽基因HERV-K降低了C57BL / 6小鼠EAE的发育，并伴随着脱髓鞘的减少和炎性细胞的抑制。此外，在这里我们测试了肽对巨噬细胞分化的影响。Env59-GPS肽的治疗通过抑制炎症性M1标志基因/细胞因子表达并增强M2相关标志物的表达来调节促炎性M1谱和抗炎性M2巨噬细胞。这些结果表明，Env59-GP3 ISU肽可能通过诱导M2巨噬细胞的极化和抑制炎症反应而在EAE中具有治疗潜力。