Semaphorins and its receptors: Emerging cellular biomarkers and therapeutic targets in autoimmune and inflammatory disorders

Semaphorins have been discovered to play an array of roles in immune regulation, especially in the complex field of inflammatory and autoimmune disorders. Originally discovered for their critical role in directing axon growth during brain development, semaphores have since been shown to have versatile actions. They are distinguished by a conserved extracellular sema domain with a 7-blade beta propeller structure. With their interactions with receptors, including neuropilins (NRP1 and NRP2) and plexins (Plexin-A1, Plexin-A4, Plexin-B1, Plexin-D1), they may substantially influence immune processes such T cell activation, thymocyte formation, dendritic cell migration and B cell clonal expansion. In this review, we intend to summarize the potential of semaphorins and their receptors as not only diagnostic biomarkers but also as promising immunotherapeutic targets. We aimed to provide an overview of the latest developments in targeting semaphorins for therapeutic intervention. These range from gene therapy to small molecule inhibitors in certain autoimmune diseases like multiple sclerosis and rheumatoid arthritis, as well as inflammatory diseases like cancer, allergic asthma and atherosclerosis. The effectiveness of targeting semaphorins to lessen inflammation and the severity of disease is already demonstrated by some preclinical research like with clinical trials focusing on SEMA3A inhibitors such as xanthofulvin and SM-345431, in case of autoimmune disorders. By addressing each patient's distinct immunological profile, minimizing side effects, and optimizing efficacy, this strategy may advance precision therapy in autoimmune and inflammatory illnesses.