The evolving role of semaphorins and plexins in the immune system: Plexin-A1 regulation of dendritic cell function

Semaphorin and plexin proteins were originally identified for their important axon guidance regulation. In recent years, their role within the immune system has been discovered. Semaphorins are considered the ligands to the plexin receptors, and together, they mediate cell–cell communication. Initially, through gene knock-out and knock-down studies, simple ligand–receptor pairings that regulate specific cellular interactions were discovered, such as between T cells and dendritic cells. However, more recent data indicate that individual cell types express multiple semaphorin and plexin proteins, engendering complex interactions involving multiple ligand–receptor pairs and multiple cell types. In this review, we describe contributions from our lab elucidating Plexin-A1 regulation of the immune system and our more recent findings of Semaphorin 6D regulation of T-cell immunity.