Novel complement receptor NRP1 augment macrophages capacity to clear apoptotic cells in C4d-dependent manner 3903

Abstract Description Apoptotic and dying cells are a major source of autoantigens and inefficient clearance of circulating self-Ag leads to activation of auto reactive B cells. Macrophages (MFs) clears dead cells and self-RNP immunocomplexes (ICs) to keeps auto-B cells in check by limiting auto-Ag availability to them. Recently, Neuropilin-1 (NRP1) has been shown to bind C4d, complement C4 activation product, which has been implicated in SLE pathogenesis. By ablating NRP1 function (antibody mediated and in-vivo NRP1 deletion) we show for the first time that NRP1 facilitate apoptotic cells clearance by MFs. By blocking C4d and NRP1 interaction, we showed that augmented apoptotic cell clearance is C4d-dependent. Unlike known complement receptor CR3 (CD11b) that facilitates receptor mediated endocytosis of complement coated ICs by macrophages (MFs), the mechanism by which NRP1 mediates clarence of ICs is not known. Internalization data shows that CR3 (CD11b) was localized to endosomal compartment of macrophages (MFs), NRP1 was confined to cell surface only suggesting NRP1 might signal differently. NRP1 deficient mice showed reduction in resident MFs population suggesting its role in maintenance and MFs survival. More experiments are required to confirm these findings. Understanding Implication of MFs specific NRP1-deficiency in autoimmune setting and augmenting MFs phagocytic function(s) could be an alternate approach to limit activation of auto reactive B cells. Funding Sources Supported by NIH R01AR074105; R01AI130307 Topic Categories Basic Autoimmunity (BA)