Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China.
Inflammopharmacology. 2018 Jun;26(3):655-665. doi: 10.1007/s10787-018-0484-y. Epub 2018 Apr 25.
Autoimmune diseases (ADs) are featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Currently, the exact pathogenesis of ADs remains not fully elucidated. Semaphorin-3A (Sema3A), a secreted member of semaphorin family, is a potent immunoregulator during all immune response stages. Sema3A has wide expression, such as in bone, connective tissue, kidney, neurons, and cartilage. Sema3A can downregulate ADs by suppressing the over-activity of both T-cell and B-cell autoimmunity. Moreover, Sema3A shows the ability to enhance T-cell and B-cell regulatory properties that control ADs, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. However, it can also induce ADs when overexpressed. Together, these data strongly suggest that Sema3A plays a pivotal role in ADs, and it may be a promising treatment target for these diseases. In the present review, we focus on the immunological functions of Sema3A and summarize recent studies on the involvement of Sema3A in the pathogenesis of ADs; the discoveries obtained from recent findings may translate into novel therapeutic agent for ADs.
自身免疫性疾病（ADs）的特征是机体的免疫反应针对自身组织，导致长期炎症和随后的组织损伤。目前，ADs 的确切发病机制仍不完全清楚。信号素-3A（Sema3A）是信号素家族的一种分泌成员，是所有免疫反应阶段的强大免疫调节剂。Sema3A 广泛表达，如骨、结缔组织、肾脏、神经元和软骨。Sema3A 可以通过抑制 T 细胞和 B 细胞自身免疫的过度活性来下调 ADs。此外，Sema3A 显示出增强 T 细胞和 B 细胞调节特性的能力，这些特性可以控制 ADs，包括系统性红斑狼疮、类风湿关节炎、多发性硬化症和全身性硬皮病。然而，当过度表达时，它也会诱导 ADs。总之，这些数据强烈表明 Sema3A 在 ADs 中发挥着关键作用，它可能是这些疾病有前途的治疗靶点。在本综述中，我们重点介绍了 Sema3A 的免疫学功能，并总结了最近关于 Sema3A 参与 ADs 发病机制的研究；最近的发现可能转化为 ADs 的新型治疗药物。
