Emerging role of semaphorin-3A in autoimmune diseases

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.