Immune semaphorins: a new area of semaphorin research

The semaphorin family comprises soluble and membrane-bound proteins originally identified as axonal guidance cues that function during neuronal development. Emerging evidence suggests that a subset of semaphorins, called 'immune semaphorins', function in the immune system. The class IV semaphorins Sema4D/CD100 and Sema4A use CD72 and Tim-2, respectively, as receptors during immune responses; these receptors comprise a set distinct from those used by semaphorins in the nervous system. Sema4D/CD100, which is expressed constitutively by T cells, is involved in the activation of B cells and dendritic cells, whereas Sema4A is preferentially expressed on B cells and dendritic cells, and is involved in the activation of T cells. Additionally, increasing evidence suggests that some other semaphorins, including viral-encoded semaphorins, might also play important roles in the immune system.