| First Author | Müller-Calleja N | Year | 2021 |
| Journal | Science | Volume | 371 |
| Issue | 6534 | PubMed ID | 33707237 |
| Mgi Jnum | J:312892 | Mgi Id | MGI:6512987 |
| Doi | 10.1126/science.abc0956 | Citation | Muller-Calleja N, et al. (2021) Lipid presentation by the protein C receptor links coagulation with autoimmunity. Science 371(6534) |
| abstractText | Antiphospholipid antibodies (aPLs) cause severe autoimmune disease characterized by vascular pathologies and pregnancy complications. Here, we identify endosomal lysobisphosphatidic acid (LBPA) presented by the CD1d-like endothelial protein C receptor (EPCR) as a pathogenic cell surface antigen recognized by aPLs for induction of thrombosis and endosomal inflammatory signaling. The engagement of aPLs with EPCR-LBPA expressed on innate immune cells sustains interferon- and toll-like receptor 7-dependent B1a cell expansion and autoantibody production. Specific pharmacological interruption of EPCR-LBPA signaling attenuates major aPL-elicited pathologies and the development of autoimmunity in a mouse model of systemic lupus erythematosus. Thus, aPLs recognize a single cell surface lipid-protein receptor complex to perpetuate a self-amplifying autoimmune signaling loop dependent on the cooperation with the innate immune complement and coagulation pathways. |
