factor for sensory fibers, and Semaphorin3C (Sema3C) and Semaphorin3F (Sema3F) repulse sympathetic nerve fibers . Whereas the primary receptor for Sema3A is neuropilin1 (NRP1), Sema3F has a higher binding affinity to neuropilin2 (NRP2). Sema3C binds to both NRP1 and NRP2 [7,8].
The action of Sema3A is not limited to the nervous system as NRP1 is expressed on endothelial cells, keratinocytes,
T cells, and tumor cells in breast and prostate cancer. Sema3A inhibits angiogenesis, migration of keratinocytes, proliferation of T cells, and migration of tumor cells [8-11]. In addition, it was recently shown that Sema3A is involved in the entry of dendritic cells to the lymphatic system . Several studies have indicated that a reduction of Sema3A expression is involved in the exacerbation of autoimmune diseases, such as RA and systemic lupus erythematosus (SLE) [13,14].
NRP1 mediates signal transduction through PlexinA coreceptors
, which are classified into four sub-families,
PlexinA1–4 . The Sema3A/NRP1/PlexinA complex regulates the actin cytoskeleton through small G-proteins, including Rac and Rho . In immune cells, the Rac family is associated with the proliferation and activation of B cells , and the activation of T cells induced by dendritic cells . NRP1 is also a putative marker of regulatory
T cells , and therefore Sema3A/NRP1/PlexinA signaling may modulate regulatory T cell functions.
Vascular endothelial growth factor165 (VEGF165), a