biostudies-literatureMeans TKNIDDK NIH HHSNCI NIH HHSNIAMS NIH HHS407-17https://www.ebi.ac.uk/biostudies/studies/S-EPMC544604biostudies-literatureUnknown115(2)Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies against nucleoproteins and DNA. Here we show that DNA-containing immune complexes (ICs) within lupus serum (SLE-ICs), but not protein-containing ICs from other autoimmune rheumatic diseases, stimulates plasmacytoid DCs (PDCs) to produce cytokines and chemokines via a cooperative interaction between Toll-like receptor 9 (TLR9) and FcgammaRIIa (CD32). SLE-ICs transiently colocalized to a subcellular compartment containing CD32 and TLR9, and CD32+, but not CD32-, PDCs internalized and responded to SLE-ICs. Our findings demonstrate a novel functional interaction between Fc receptors and TLRs, defining a pathway in which CD32 delivers SLE-ICs to intracellular lysosomes containing TLR9, inducinThe Journal of clinical investigationHuman lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.PMC5446045T32AR07258P01-DK50305P01 DK050305R01-CA69212T32 AR007258R01 CA069212Luster ADMeans TKGolenbock DTHayashi FMurali MRLatz EfalseHuman lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies against nucleoproteins and DNA. Here we show that DNA-containing immune complexes (ICs) within lupus serum (SLE-ICs), but not protein-containing ICs from other autoimmune rheumatic diseases, stimulates plasmacytoid DCs (PDCs) to produce cytokines and chemokines via a cooperative interaction between Toll-like receptor 9 (TLR9) and FcgammaRIIa (CD32). SLE-ICs transiently colocalized to a subcellular compartment containing CD32 and TLR9, and CD32+, but not CD32-, PDCs internalized and responded to SLE-ICs. Our findings demonstrate a novel functional interaction between Fc receptors and TLRs, defining a pathway in which CD32 delivers SLE-ICs to intracellular lysosomes containing TLR9, inducin2005-01-01T00:00:00Z2005 Feb2025-04-20T01:34:41.243Z2019-03-27T01:08:30ZS-EPMC5446041566874010.1172/jci20052302510.1172/JCI23025