Kuklina Elena
Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences, Perm, Russia.
Int Rev Immunol. 2021;40(4):268-273. doi: 10.1080/08830185.2021.1905807. Epub 2021 Mar 31.
Semaphorin 4D (Sema4D) is a classic member of the semaphorin family involved in axonal guidance processes. The key effects of Sema4D in neurons are mediated by high affinity plexin receptors and are associated with cytoskeleton rearrangement, leading to growth cone collapse or regulation of cell migration. Along with this, the semaphorin is widely represented in the immune system and has a pronounced immunoregulatory activity. The involvement of Sema4D in the control of immune cell migration was shown almost twenty years ago, in one of the first studies of semaphorin. The emergence of such work was quite predictable, since the most well-known effects of Sema4D outside the immune system were associated precisely with the control of cell motility. However, after identification of CD72 as a specific Sema4D receptor in the immune system, studies of the immunoregulatory activity of semaphorin focused on its CD72-dependent effects unrelated to cytoskeleton rearrangement, and this trend continues up to now. Nevertheless, a number of recent studies demonstrating the presence of plexin receptors for Sema4D in the immune system forces us to return to the question of whether this semaphorin can play its classic role of a guidance molecule in relation to immune cells too. The review discusses Sema4D involvement in the control of immune cell migration, as well as the mechanisms of these effects and their potential contribution to the development and function of immune system.
信号素4D（Sema4D）是信号素家族的经典成员，参与轴突导向过程。Sema4D在神经元中的关键作用由高亲和力的丛状蛋白受体介导，并与细胞骨架重排有关，导致生长锥塌陷或调节细胞迁移。与此同时，信号素在免疫系统中广泛存在，并具有显著的免疫调节活性。大约20年前，在信号素的首批研究之一中，就显示了Sema4D参与免疫细胞迁移的控制。这项工作的出现是相当可预测的，因为Sema4D在免疫系统之外最著名的作用恰恰与细胞运动的控制有关。然而，在确定CD72为免疫系统中Sema4D的特异性受体后，信号素免疫调节活性的研究集中在其与细胞骨架重排无关的CD72依赖性效应上，这一趋势一直持续到现在。尽管如此，最近的一些研究表明免疫系统中存在Sema4D的丛状蛋白受体，这迫使我们重新审视这个信号素是否也能在免疫细胞中发挥其作为导向分子的经典作用。这篇综述讨论了Sema4D参与免疫细胞迁移的控制，以及这些效应的机制及其对免疫系统发育和功能的潜在贡献。
