Dietary interventions such as fasting have been proved to be effective in the prevention of metabolic and autoimmune diseases as well as aging-related conditions. The complicated interaction between nutrition and immunity has drawn wide attention in recent years. In this study, we investigated the therapeutic effect of intermittent caloric restriction on autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, in mice. EAE was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein 35–55 peptide. After the EAE symptoms became obvious at the 4th week post-immunization, the mice were administered with a modified fasting-mimicking diet (FMD) at 1/3 cal of control for 3 days, followed by ad libitum with normal chow for 4 days. A total of two cycles of FMD was applied. Compared with the mice without receiving caloric restriction, the mice using FMD had significant decreases in EAE severity, immune cell infiltration in spinal cord and CNS demyelination. FMD administration also reversed EAE-mediated CNS accumulation of total CD4+ T cells and in particular, IFN-γ-producing CD4+ T cells. Moreover, FMD application elevated the cell proliferation rate in CNS and enhanced expression of brain-derived neurotrophic factor (BDNF) and remyelination markers. In conclusion, our results indicate that intermittent caloric restriction using the modified FMD was effective in the treatment of EAE through ameliorating inflammatory response and promoting recovery of the damaged tissue.

已证明禁食等饮食干预措施可有效预防代谢和自身免疫性疾病以及与衰老相关的疾病。近年来，营养与免疫之间复杂的相互作用引起了广泛关注。在这项研究中，我们研究了间歇性热量限制对小鼠自身免疫性脑脊髓炎 (EAE)（一种多发性硬化症模型）的治疗效果。EAE 是通过用髓鞘少突胶质细胞糖蛋白 35-55 肽免疫 C57BL/6 小鼠来诱导的。在免疫后第 4 周 EAE 症状变得明显后，小鼠以 1/3 cal 对照的改良禁食模拟饮食 (FMD) 给药 3 天，然后随意正常饮食4天。总共应用了两个循环的 FMD。与未接受热量限制的小鼠相比，使用 FMD 的小鼠的 EAE 严重程度、脊髓免疫细胞浸润和中枢神经系统脱髓鞘显着降低。FMD 给药还逆转了 EAE 介导的 CNS 总 CD4+ T 细胞的积累，特别是产生 IFN-γ 的 CD4+ T 细胞。此外，FMD 应用提高了 CNS 中的细胞增殖率，并增强了脑源性神经营养因子 (BDNF) 和髓鞘再生标志物的表达。总之，我们的结果表明，使用改良 FMD 的间歇性热量限制通过改善炎症反应和促进受损组织的恢复，可有效治疗 EAE。