Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran; Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Int Immunopharmacol. 2021 Jun;95:107556. doi: 10.1016/j.intimp.2021.107556. Epub 2021 Mar 20.
The immune and nervous systems possess a highly intricate network of synaptic connections, shared messenger molecules, and exquisite communication ways, allowing intercellular signal transduction. The semaphorins (Semas) were initially identified as axonal guidance molecules in the development of the nervous system but later were found to be implicated also in regulating the immune system, known in this case as the "immune Semas" or "immunoregulatory Semas". Increasingly, these molecules are involved in multiple aspects of both physiological and pathological immune responses and were recently indicated to take part in various immunological disorders, encompassing allergy, cancer, and autoimmunity. Semas transduce signals by connecting to their cognate receptors, namely, plexins and neuropilins. Some of them, like Sema-3F, have been found to function as the inducer of the remyelination process whereas some others, like Sema-3A and Sema-4D, act to inhibit this process, either directly or indirectly. Besides, Sema-4A is crucial to the differentiation of T helper type 1 (Th1) and Th17 cells that are potentially involved in the pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central nervous system. This review aims to reveal the role of immune Semas in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis, focusing on the therapeutic usages of these molecules to treat this neurodegenerative disease.
免疫系统和神经系统拥有高度复杂的突触连接网络、共享的信使分子和精细的通讯方式，从而实现细胞间信号转导。信号素（Semas）最初被鉴定为神经系统发育中的轴突导向分子，但后来发现它们也参与调节免疫系统，在这种情况下被称为“免疫信号素”或“免疫调节信号素”。这些分子越来越多地参与生理和病理免疫反应的多个方面，最近还表明它们参与各种免疫性疾病，包括过敏、癌症和自身免疫。Semas 通过与它们的同源受体（即神经丛蛋白和神经纤毛蛋白）连接来传递信号。其中一些，如 Sema-3F，已被发现作为髓鞘再生过程的诱导剂，而另一些，如 Sema-3A 和 Sema-4D，则直接或间接地抑制该过程。此外，Sema-4A 对 T 辅助细胞 1（Th1）和 Th17 细胞的分化至关重要，Th1 和 Th17 细胞可能参与多发性硬化症（MS）的发病机制，MS 是一种中枢神经系统自身免疫性疾病。本综述旨在揭示免疫信号素在 MS 及其动物模型实验性自身免疫性脑脊髓炎发病机制中的作用，重点介绍这些分子在治疗这种神经退行性疾病中的治疗用途。
