Immune semaphorins: Crucial regulatory signals and novel therapeutic targets in asthma and allergic diseases

Asthma and allergic diseases are a group of chronic inflammatory disorders that arise as a result of excessive responses of the immune system against intrinsically harmless environmental substances. It is well known that substantial joint characteristics exist between the immune and nervous systems. The semaphorins (Semas) were initially characterized as axon-guidance molecules that play a crucial role during the development of the nervous system. However, increasing evidence indicates that a subset of Semas, termed "immune Semas", acting through their cognate receptors, namely, plexins (Plxns), and neuropilins (Nrps), also contributes to both physiological and pathological responses of the immune system. Notably, immune Semas exert critical roles in regulating a broad spectrum of biological processes, including immune cell-cell interactions, activation, differentiation, cell migration and mobility, angiogenesis, tumor progression, as well as inflammatory responses. Accumulating evidence indicates that the modification in the signaling of immune Semas could lead to various immunemediated inflammatory diseases, ranging from cancer to autoimmunity and allergies. This review summarizes the recent evidence regarding the role of immune Semas in the pathogenesis of asthma and allergic diseases and discusses their therapeutic potential for treating these diseases.