Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Neurology, Farabi Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Gene. 2020 Jul 1;746:144637. doi: 10.1016/j.gene.2020.144637. Epub 2020 Mar 31.
Semaphorins are a group of proteins that are divided into eight subclasses and identified by a conserved Sema domain on their carboxyl terminus. Sema4A, 4C, and 4D are the members of the fourth class of semaphorin family, which are known as membrane semaphorins; however, these molecules can be altered to soluble semaphorins by proteolytic cleavage. Semaphorins have various roles in the immune, nervous, and metabolic systems. In the immune system, these molecules contribute to the formation of cellular, humoral, and innate immune responses, such as inflammation, leukocyte migration, immunological synapse formation, and germinal center events. Given the diverse roles of semaphorins in the immune system, in this review, we have tried to give a comprehensive look at the role of these molecules in autoimmunity, allergy, and cancer. Sema4D and 4A seem to play a critical role in the pathogenesis of some autoimmune diseases, such as multiple sclerosis. In contrast, it has been shown that Sema4A and 4C have beneficial effects on allergies, and their absence can exacerbate the severity of the disease. In the case of cancer, an increase in all three of these molecules has been reported. Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood. In conclusion, semaphorins seem to be a favorable therapeutic target for autoimmune diseases and allergies. However, in cancer, studies have not yet been able to identify the exact role of semaphorins, and further studies are needed.
信号蛋白是一组蛋白质，根据其羧基末端保守的 Sema 结构域，可分为八个亚类。Sema4A、4C 和 4D 是信号蛋白家族第四类的成员，被称为膜信号蛋白；然而，这些分子可以通过蛋白水解切割转化为可溶性信号蛋白。信号蛋白在免疫、神经和代谢系统中具有多种功能。在免疫系统中，这些分子有助于细胞、体液和先天免疫反应的形成，如炎症、白细胞迁移、免疫突触形成和生发中心事件。鉴于信号蛋白在免疫系统中的多种作用，在这篇综述中，我们试图全面了解这些分子在自身免疫、过敏和癌症中的作用。Sema4D 和 4A 似乎在一些自身免疫性疾病（如多发性硬化症）的发病机制中发挥关键作用。相比之下，已经表明 Sema4A 和 4C 对过敏有有益的影响，其缺失会加重疾病的严重程度。在癌症的情况下，已经报道了所有这三种分子的增加。Sema4D 和 4C 可以促进人类患者或实验模型中的肿瘤进展，而 Sema4A 的作用尚未完全理解。总之，信号蛋白似乎是自身免疫性疾病和过敏的一个有利的治疗靶点。然而，在癌症中，研究尚未能够确定信号蛋白的确切作用，需要进一步的研究。
