Abstract

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.

摘要

Semaphorin 4D (Sema4D) 是参与轴突引导过程的信号蛋白家族的经典成员。Sema4D 在神经元中的关键作用是由高亲和力 plexin 受体介导的，并且与细胞骨架重排有关，导致生长锥塌陷或细胞迁移的调节。与此同时，信号素在免疫系统中广泛存在，并具有显着的免疫调节活性。大约 20 年前，Sema4D 参与了对免疫细胞迁移的控制，这是对信号素的首批研究之一。这种工作的出现是完全可以预见的，因为 Sema4D 在免疫系统之外的最著名的作用与细胞运动的控制精确相关。然而，在将 CD72 鉴定为免疫系统中的特异性 Sema4D 受体后，semaphorin 的免疫调节活性研究集中在其与细胞骨架重排无关的 CD72 依赖性作用上，这一趋势一直持续到现在。然而，最近的一些研究表明免疫系统中存在 Sema4D 的丛蛋白受体，这迫使我们回到这个问题上，即这种信号蛋白是否也可以发挥其与免疫细胞相关的指导分子的经典作用。该综述讨论了 Sema4D 参与控制免疫细胞迁移，以及这些作用的机制及其对免疫系统发育和功能的潜在贡献。最近的一些研究表明免疫系统中存在 Sema4D 的丛蛋白受体，这迫使我们回到这个问题上，即这种信号蛋白是否也可以发挥其与免疫细胞相关的指导分子的经典作用。该综述讨论了 Sema4D 参与控制免疫细胞迁移，以及这些作用的机制及其对免疫系统发育和功能的潜在贡献。最近的一些研究表明免疫系统中存在 Sema4D 的丛蛋白受体，这迫使我们回到这个问题上，即这种信号蛋白是否也可以发挥其与免疫细胞相关的指导分子的经典作用。该综述讨论了 Sema4D 参与控制免疫细胞迁移，以及这些作用的机制及其对免疫系统发育和功能的潜在贡献。