中枢神经系统来源的白细胞介素-6可能以细胞依赖的方式影响实验性自身免疫性脑脊髓炎的发病机制。
Interleukin-6 Derived from the Central Nervous System May Influence the Pathogenesis of Experimental Autoimmune Encephalomyelitis in a Cell-Dependent Manner.
机构信息
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Current affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University Irving Medical Center, New York, NY10032, USA.
出版信息
Cells. 2020 Jan 31;9(2):330. doi: 10.3390/cells9020330.
BACKGROUND
Interleukin-6 (IL-6) is a pleiotropic and multifunctional cytokine that plays a critical role in induction of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Although EAE has always been considered a peripherally elicited disease, Il6 expression exclusively within central nervous system is sufficient to induce EAE development. Neurons, astrocytes, and microglia can secrete and respond to IL-6.
METHODS
To dissect the relevance of each cell source for establishing EAE, we generated and immunized conditional Il6 knockout mice for each of these cell types with myelin oligodendrocyte glycoprotein 35-55 (MOG) peptide dissolved in complete Freund's adjuvant (CFA) and supplemented with Mycobacterium tuberculosis.
RESULTS AND CONCLUSIONS
The combined results reveal a minor role for Il6 expression in both astrocytes and microglia for symptomatology and neuropathology of EAE, whereas neuronal Il6 expression was not relevant for the variables analyzed.
背景
白细胞介素-6（IL-6）是一种多效性和多功能细胞因子，在实验性自身免疫性脑脊髓炎（EAE）的诱导中起着关键作用，EAE 是多发性硬化症（MS）的小鼠模型。尽管 EAE 一直被认为是一种外周引发的疾病，但仅在中枢神经系统内表达的 Il6 足以诱导 EAE 的发展。神经元、星形胶质细胞和小胶质细胞均可分泌和响应 IL-6。
方法
为了剖析每种细胞来源在建立 EAE 中的相关性，我们生成并免疫了条件性 Il6 敲除小鼠，这些细胞类型分别用髓鞘少突胶质细胞糖蛋白 35-55（MOG）肽溶解于完全弗氏佐剂（CFA）中，并添加分枝杆菌结核佐剂。
结果与结论
综合结果表明，Astrocytes 和小胶质细胞中的 Il6 表达对 EAE 的症状和神经病理学的影响较小，而神经元中的 Il6 表达与分析的变量无关。
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