Immune regulatory mechanisms of neuropilins and its receptors

Abstract

Neuropilins (NRP) are co-receptors for class 3 semaphorins (Sema) and members of the vascular endothelial growth factor (VEGF) family of angiogenic cytokines. Genetic analysis of the role of NRP in mice shows that NRP1 is essential for embryonic neuronal pathfinding and cardiovascular development, which is mediated via Sema and VEGF, respectively. NRP are thought to mediate functional responses, especially cell migration, as a result of complex formation with other receptors, such as plexins in the case of Sema and the VEGF receptor (VEGFR)2, resulting in enhanced signaling via some intracellular pathways. Recent findings indicate that NRP may play important biological roles in other physiological and disease-related processes. In particular, NRP are highly expressed in diverse tumour cell lines and human neoplasms. NRP also implicate in several biological processes regulating tumour growth in vivo, suggesting that NRP1 may be a future therapeutic target in cancer. In the immune system, NRP1 acts as a negative regulator of the immune system via Sema3A and it may be a therapeutic target in autoimmune diseases. In this article, we will review the immune regulatory mechanisms of NRP and its receptors. Key words: Neuropilins; Semaphorins; Vascular endothelial growth factor; Immune regulation