1. Figure 4 Involvement of SEMA4D in the pathogenesis
of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
Figure 4 | Involvement of SEMA4D in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In healthy conditions, the interaction between the plexin B2 ligand on endothelial cells and the SEMA4D receptor on the surface of neutrophils inhibits RAS-related C3 botulinum toxin substrate (RAC1) activation in neutrophils and negatively regulates neutrophil activation. By contrast, in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), SEMA4D is proteolytically cleaved from the surface of neutrophils. Alterations in SEMA4D–plexin B2 interactions results in inappropriate activation of neutrophils such as Toll-like receptor (TLR) ligand-induced or ANCA-induced neutrophil extracellular trap (NET) formation, and is involved in the pathogenesis of AAV. ADAM17, disintegrin and metalloproteinase 17.
Nishide, M. & Kumanogoh, A. (2017) The role of semaphorins in immune responses and autoimmune rheumatic diseases
Nat. Rev. Rheumatol. doi: /nrrheum