Reversal of paralysis and reduced inflammation from peripheral administration of β-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.
Reversal of paralysis and reduced inflammation from peripheral administration of β-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.
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DOI：
10.1126/scitranslmed.3004145
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发表时间：
2012-08-01
影响因子：
17.1
通讯作者：
Steinman L
中科院分区：
文献类型：
--
作者：
Grant JL;Ghosn EE;Axtell RC;Herges K;Kuipers HF;Woodling NS;Andreasson K;Herzenberg LA;Herzenberg LA;Steinman L
β-淀粉样蛋白-42(A-β42)和β-淀粉样蛋白-40(Aβ40)是阿尔茨海默病(AD)中老年斑沉积的主要成分，被认为具有神经毒性和促炎作用。在多发性硬化症(MS)中，Aβ42在脑部病变和受损的轴突中上调。在这里，我们意外地发现，在四种不同的实验性自身免疫性脑脊髓炎(EAE)模型中，Aβ42或Aβ40肽的治疗减少了运动瘫痪和脑部炎症，缓解了运动瘫痪，减少了中枢神经系统的炎性损害，并抑制了淋巴细胞的激活。Aβ42和Aβ40治疗可有效减少过继转移自身反应性Th1或Th17细胞所致的持续瘫痪。体内Aβ42和Aβ40治疗后外周免疫细胞群体的高维14参数流式细胞术显示，在EAE期间淋巴系和髓系亚群的百分比有显著的调节。经Aβ肽治疗后，血液中主要的促炎细胞因子和趋化因子减少。Aβ治疗提供的保护不需要将其输送到大脑：通过过继转移来自经Aβ42治疗的供者的淋巴细胞可以减弱WT受体小鼠的EAE，免疫组织化学分析未在治疗的EAE小鼠的脑中检测到Aβ沉积。与A-β治疗对EAE的改善相比，淀粉样前体蛋白基因缺失的小鼠的EAE更差。因此，在缺乏Aβ的情况下，会加剧临床上EAE疾病的进展。由于Aβ42和Aβ40可以改善以中枢神经系统为靶点的实验性自身免疫性炎症，我们现在可以考虑它在其他神经病理条件下的潜在抗炎作用。
β-amyloid-42 (Aβ42) and β-amyloid-40 (Aβ40), major components of senile plaque deposits in Alzheimer’s disease (AD), are considered neurotoxic and pro-inflammatory. In multiple sclerosis (MS), Aβ42 is upregulated in brain lesions and damaged axons. Here we found, unexpectedly, that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. Aβ42 and Aβ40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive Th1 or Th17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo Aβ42 and Aβ40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major pro-inflammatory cytokines and chemokines were reduced in the blood following Aβ peptide treatment. Protection conferred by Aβ treatment did not require its delivery to the brain: adoptive transfer with lymphocytes from donors treated with Aβ42 attenuated EAE in WT recipient mice and Aβ deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with Aβ-treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of Aβ there is exacerbated clinical EAE disease progression. Since Aβ42 and Aβ40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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