Neuropilins and semaphorins — from angiogenesis to autoimmunity

Angiogenesis, the growth of new blood vessels from preexisting ones, is an important process in health and disease. The persistence of neovascularization in inflammatory diseases, such as rheumatoid arthritis (RA), might facilitate the entrance of inflammatory cells into the synovium and stimulate pannus formation. Several potent pro-angiogenic cytokines have been implicated in inflammatory angiogenesis. Of these, vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been demonstrated to play a central role in RA, systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Increased serum levels of VEGF were found to correlate with disease activity and severity of these diseases whereas, remission was associated with decreased levels. In the last few years, other molecules, initially found in neurodevelopment, were found to be involved in angiogenesis and recently also in the immune system and autoimmunity. Neuropilins (NPs) are VEGF receptors, while some of the semaphorins (SEMAs) are neuropilinsʹ ligands. Their involvement in the development of autoimmune diseases and the various mechanisms by which they may induce autoimmunity will be discussed in this review.