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Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages
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Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages
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Journal Article
Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages
2016
Overview
Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine, has been shown to affect inflammation in some experimental models. We show here that spermidine could alleviate experimental autoimmune encephalomyelitis (EAE), a model for MS, through regulating the infiltration of CD4
+
T cells and macrophages in central nervous system. Unexpectedly, we found that spermidine treatment of MOG-specific T cells did not affect their pathogenic potency upon adaptive transfer; however, spermidine diminished the ability of macrophages in activating MOG-specific T cells
ex vivo
. Depletion of macrophages in diseased mice completely abolished the therapeutic effect of spermidine, indicating a critical role of spermidine-activated macrophages. Mechanistically, spermidine was found to specifically suppress the expression of interleukin-1beta (IL-1
β
), IL-12 and CD80 while enhance the expression of arginase 1 in macrophages. Interestingly, macrophages from spermidine-treated mice could also reverse EAE progression, while pretreatment of those macrophages with the arginase 1 inhibitor abrogated the therapeutic effect. Therefore, our studies revealed a critical role of macrophages in spermidine-mediated treatment on EAE and provided novel information for better management of MS.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/21
/ 13/31
/ 13/51
/ 38/39
/ 38/61
/ 631/250
/ 64/60
/ Animals
/ Antigens
/ Biomedical and Life Sciences
/ Cell Polarity - drug effects
/ Central Nervous System - immunology
/ Central Nervous System - pathology
/ Disease
/ Encephalomyelitis, Autoimmune, Experimental - drug therapy
/ Encephalomyelitis, Autoimmune, Experimental - pathology
/ Encephalomyelitis, Autoimmune, Experimental - prevention & control
/ Medicine
/ Signal Transduction - drug effects
