Human lupus autoantibody–DNA complexes activate DCs through cooperation of CD32 and TLR9
Massachusetts General Hospital · University of Massachusetts Chan Medical School
Abstract
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…
Citation impact
- FWCI
- 21.54
- Percentile
- 100%
- References
- 59
Authors
6Topics & keywords
- TLR9
- Autoantibody
- Immunology
- Toll-Like Receptor 9
- Systemic lupus erythematosus
- Immune system
- Autoimmune disease
- Innate immune system
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