Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection
Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection
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DOI：
10.1016/j.expneurol.2017.10.008
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发表时间：
2018-01-01
影响因子：
5.3
通讯作者：
Ben-Hur, Tamir
中科院分区：
文献类型：
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作者：
Einstein, Ofira;Fainstein, Nina;Ben-Hur, Tamir
背景资料：运动训练（ET）对实验性自身免疫性脑脊髓炎（EAE）的影响有明确的结果，运动对疾病进展的影响也不清楚。Objective：我们研究了ET是否通过调节全身免疫系统或对CNS产生直接的神经保护作用来改善EAE的发展。采用蛋白脂质蛋白（PLP）诱导的小鼠转移性EAE模型。为了评估ET对系统性自身免疫的影响，将来自训练的与久坐的供体小鼠的淋巴结（LN）-T细胞转移到幼稚受体。为了评估ET的直接神经保护作用，将PLP反应性LN-T细胞转移到在EAE转移之前训练的受体小鼠或久坐小鼠中。EAE的严重程度进行了评估，在体内和致脑炎的LN-T细胞的特性来自PLP免疫小鼠进行了评估，在vitro.Results：LN-T细胞从训练的小鼠中获得诱导一个衰减的临床和病理EAE受体小鼠与来自久坐的动物细胞。训练抑制了PLP反应性T细胞对中枢神经系统衍生自身抗原的激活、增殖和细胞因子基因表达，但强烈增强了它们对伴刀豆球蛋白A（一种非特异性刺激）的增殖。然而，有EAE的严重程度没有差异时，自身反应性致脑炎T细胞被转移到训练与久坐recipientmice.Conclusion：ET抑制免疫系统对自身抗原的反应，以减轻EAE，而不是一般抑制免疫系统，但不诱导对EAE的直接神经保护作用。
Background: Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression.Objective: We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS.Methods: Healthy mice were subjected to 6 weeks of motorized treadmill running. The Proteolipid protein (PLP)induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naive recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro.Results: LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice.Conclusion: ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE.