IL-7Rα 赋予实验性自身免疫性脑脊髓炎易感性。
IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis.
机构信息
Neuroscience Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
出版信息
Genes Immun. 2011 Jan;12(1):1-14. doi: 10.1038/gene.2010.49. Epub 2010 Sep 23.
Abstract
Multiple sclerosis (MS) is a neurological disorder that causes paralysis in young adults and affects women more frequently than men. The etiology of MS is not known, but it is generally viewed as an autoimmune disease of the central nervous system (CNS), influenced by genetic and environmental factors. Recent studies have identified interleukin-7 receptor α (IL-7Rα) as a risk factor for MS. But the role of IL-7Rα in experimental autoimmune encephalomyelitis (EAE) model of MS is not known. In this study we demonstrate that IL-7Rα-deficient (IL-7Rα(-/-)) mice remain resistant to MOGp35-55-induced EAE. When compared with C57BL/6 wild-type mice, IL-7Rα(-/-) mice showed less severe inflammation and demyelination in the CNS. The attenuation of EAE in IL-7Rα(-/-) mice was associated with a decrease in T-helper (Th) 1 and Th17 responses in the CNS and lymphoid organs. IL-7Rα(-/-) mice also showed an increase in Th2 response and CD4(+)Foxp3(+) regulatory T cells. These findings highlight that IL-7Rα confers susceptibility by influencing autoimmune Th1/Th17 responses in EAE model of MS.
摘要
多发性硬化症（MS）是一种神经系统疾病，会导致年轻人瘫痪，且女性发病率高于男性。MS 的病因尚不清楚，但通常被认为是中枢神经系统（CNS）的自身免疫性疾病，受遗传和环境因素的影响。最近的研究表明白细胞介素-7 受体 α（IL-7Rα）是 MS 的一个风险因素。但 IL-7Rα 在 MS 的实验性自身免疫性脑脊髓炎（EAE）模型中的作用尚不清楚。在这项研究中，我们证明了 IL-7Rα 缺陷（IL-7Rα(-/-)）小鼠仍然对 MOGp35-55 诱导的 EAE 具有抗性。与 C57BL/6 野生型小鼠相比，IL-7Rα(-/-) 小鼠在中枢神经系统中表现出较轻的炎症和脱髓鞘。IL-7Rα(-/-) 小鼠 EAE 的减轻与中枢神经系统和淋巴器官中 Th1 和 Th17 反应的减少有关。IL-7Rα(-/-) 小鼠还显示出 Th2 反应和 CD4(+)Foxp3(+)调节性 T 细胞的增加。这些发现强调了 IL-7Rα 通过影响 MS 的 EAE 模型中的自身免疫性 Th1/Th17 反应赋予易感性。
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Hum Genet. 2010 Mar;127(5):525-35. doi: 10.1007/s00439-010-0789-4. Epub 2010 Jan 30.
2
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Nat Immunol. 2009 Nov;10(11):1178-84. doi: 10.1038/ni.1791. Epub 2009 Sep 27.
3
Risk alleles for multiple sclerosis in multiplex families.复杂家系中多发性硬化症的风险等位基因。
Neurology. 2009 Jun 9;72(23):1984-8. doi: 10.1212/WNL.0b013e3181a92c25.
4
Curing CNS autoimmune disease with myelin-reactive Foxp3+ Treg.用髓鞘反应性Foxp3 +调节性T细胞治疗中枢神经系统自身免疫性疾病。
Eur J Immunol. 2009 Apr;39(4):1108-17. doi: 10.1002/eji.200839073.
5
Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients.德国多发性硬化症患者中IL7RA和IL2RA基因的变异
J Autoimmun. 2009 Mar;32(2):110-5. doi: 10.1016/j.jaut.2009.01.002. Epub 2009 Feb 23.
6
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J Immunol. 2008 Oct 15;181(8):5681-90. doi: 10.4049/jimmunol.181.8.5681.
7
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8
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9
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