6533b851fe1ef96bd12a8f85
RESEARCH PRODUCT
Lipid presentation by the protein C receptor links coagulation with autoimmunity.
Wolfram RufWolfram RufCharles T. EsmonAnna EtzoldAnne HollerbachJulia Weinmann-menkeDennis StrandSusanne StrandThati MadhusudhanMyriam MeineckJohannes BraunNadine Müller-callejaNadine Müller-callejaJian-ming GuMarkus P. RadsakFriederike HäuserKai BrunsDenise PedrosaAntje CanisiusKarl J. LacknerUlrich ZechnerJennifer RoyceT. Son NguyenLuc TeytonSvenja RitterSina Teifelsubject
Receptor complexAntigen presentationAutoimmunityEndosomesmedicine.disease_causeArticleAutoimmunityMiceInterferonimmune system diseasesmedicineAnimalsHumansLupus Erythematosus SystemicneoplasmsBlood CoagulationAutoantibodiesAutoimmune diseaseEndothelial protein C receptorAntigen PresentationMultidisciplinaryInnate immune systemLupus erythematosusEndothelial Protein C ReceptorThrombosismedicine.diseaseAntiphospholipid SyndromeImmunity InnateMice Mutant StrainsDisease Models AnimalSphingomyelin PhosphodiesteraseToll-Like Receptor 7ImmunologyAntibodies AntiphospholipidEmbryo LossMonoglyceridesEndothelium VascularLysophospholipidsmedicine.drugdescription
A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antiphospholipid antibodies (aPLs). These molecules can activate the complement and coagulation cascades, which contributes to pathologies such as thrombosis, stroke, and pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is the cell-surface target for aPL and mediates its internalization (see the Perspective by Kaplan). aPL binding to EPCR-LBPA resulted in the activation of tissue factor–mediated coagulation and interferon-α production by dendritic cells. Interferon-α, in turn, fueled the expansion of B1a cells, which secrete aPLs. The specific blockade of this target in mice inhibited the development of aPL autoimmunity, offering hope for future therapies for these conditions. Science , this issue p. eaay1833 ; see also p. 1100
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-03-12 | Science (New York, N.Y.) |