| Literature DB >> 33707237 |
Nadine Müller-Calleja1,2,3, Anne Hollerbach1,2, Jennifer Royce3, Svenja Ritter2, Denise Pedrosa1, Thati Madhusudhan1, Sina Teifel2, Myriam Meineck4, Friederike Häuser2, Antje Canisius2, T Son Nguyen1, Johannes Braun1, Kai Bruns2, Anna Etzold5,6, Ulrich Zechner5,6, Susanne Strand4, Markus Radsak7, Dennis Strand4, Jian-Ming Gu8, Julia Weinmann-Menke4, Charles T Esmon8, Luc Teyton3, Karl J Lackner9, Wolfram Ruf10,3.
Abstract
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.Entities:
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Year: 2021 PMID： 33707237 PMCID： PMC9014225 DOI： 10.1126/science.abc0956
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714