Diverse roles for semaphorin−plexin signaling in the immune system

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several semaphorins, so-called ‘immune semaphorins’, are crucially involved in various phases of both physiological and pathological immune responses; some regulate immune cell activation or differentiation, whereas others navigate the trafficking of immune cells. Plexin family members are one of the most representative semaphorin receptors and the semaphorin–plexin complex structures were recently determined in crystallization studies. Here, we review the rapidly emerging functions of semaphorins and their receptors in the immune system.