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阐明神经抗原与遗传多样性对 MP4 诱导的 C57BL/6 和 B6.129 小鼠实验性自身免疫性脑脊髓炎的影响。

Delineating the impact of neuroantigen vs genetic diversity on MP4-induced EAE of C57BL/6 and B6.129 mice.

机构信息

Department of Anatomy I, University of Cologne, Cologne, Germany.

出版信息

APMIS. 2009 Dec;117(12):923-35. doi: 10.1111/j.1600-0463.2009.02555.x.

Abstract

MBP-PLP fusion protein (MP4)-induced experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis (MS) that encompasses both a time-dependent attack on central nervous system (CNS) regions and a B cell component, mirroring important features of human multiple sclerosis. Comparing C57BL/6 with B6.129 mice immunized with MP4, we point out similarities regarding these hallmarks and thus propose that they are largely dependent on the nature of the MP4 antigen itself, while differences between the two strains suggest that additional fine-tuning is brought about by the genetic repertoire of the animal. Overall, our data imply that (i) the interplay between both the antigenic trigger and genetic variables can define the outcome of MP4-induced autoimmune encephalomyelitis in C57BL/6 and B6.129 mice and (ii) that MP4 is not only a strong neuroantigen when it comes to reproducing the dynamics in effector mechanisms as is typical of the disease but also a promising agent for studying interindividual heterogeneity derived from genetic diversity in EAE/MS.

摘要

MBP-PLP 融合蛋白 (MP4) 诱导的实验性自身免疫性脑脊髓炎 (EAE) 是多发性硬化症 (MS) 的模型,它包括对中枢神经系统 (CNS) 区域的时间依赖性攻击和 B 细胞成分,反映了人类多发性硬化症的重要特征。我们比较了用 MP4 免疫的 C57BL/6 与 B6.129 小鼠,指出了这些特征的相似之处,因此我们提出,这些特征主要取决于 MP4 抗原本身的性质,而这两个品系之间的差异表明,动物的遗传基因库带来了额外的微调。总的来说,我们的数据表明:(i) 抗原触发和遗传变量之间的相互作用可以决定 C57BL/6 和 B6.129 小鼠中 MP4 诱导的自身免疫性脑脊髓炎的结果;(ii) MP4 不仅是一种强大的神经抗原,能够重现疾病中典型的效应机制动力学,而且是研究多发性硬化症/自身免疫性脑脊髓炎中遗传多样性带来的个体间异质性的有前途的工具。

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