Multiple sclerosis (MS) is one of the chronic and debilitating autoimmune diseases, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine produced during arginine metabolism, was shown to alleviate experimental autoimmune encephalitis (EAE), a mouse model of MS.

A research team led by Drs. SHI Yufang and CAO Wei at the Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine found that spermidine administration suppresses EAE progression by inhibiting the pro-inflammatory activity of macrophages, rather than directly regulating pathogenic myelin-responsive T cells.

When the spermidine pre-treated disease causing T cells were transferred into normal mice, those T cells can still establish classical EAE with similar clinical score to that of control MOG-reactivated T cells. However, when macrophages were depleted, the therapeutic effect of spermidine was abolished.

Two pathways were identified to be involved in the regulation of macrophages by spermidine. One is spermidine endows macrophages with the immunosuppression capacity through inhibiting NF-κB signaling. The other is spermidine upregulates arginase 1 expression in macrophages, which confers these macrophages with the therapeutic effect on EAE.

Taken together, this study revealed that spermidine exerts its therapeutic effect on EAE through regulating macrophages and provided novel information for better management of MS. The study entitled “Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages” was published online in Cell Death & Differentiation.

This work was supported by grants from National Natural Science Foundation of China, Ministry of Science and Technology of China and Chinese Academy of Sciences.