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.
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