The role of Sema4A in angiogenesis, immune responses, carcinogenesis, and retinal systems

Semaphorins were originally identified as axon guidance cues that regulate the functional activity of axons in the nervous system. In addition, accumulating evidence indicates that semaphorins have multiple functions in physiological and pathogenic processes, including vascular development, tumor progression, and immune responses. Sema4A is a semaphorin expressed in immune cells, and is thus termed an “immune semaphorin.” Sema4A has 4 types of receptors: Plexin D family, Plexin B family, Tim-2, and Nrp-1. Recent studies suggest that Sema4A plays critical roles in many processes including cell–cell interactions, immune-cell activation, differentiation, and migration. In other studies, Sema4A is also associated with carcinogenesis and retinal systems. In this review, we summarize current knowledge regarding the biology of Sema4A in relation to angiogenesis, immune responses, colorectal cancer, and the retina.