Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Copyright policy )Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Increased concentrations of DNA-containing immune complexes in the serum are associated with systemic autoimmune diseases such as lupus. Stimulation of Toll-like receptor 9 (TLR9) by DNA is important in the activation of plasmacytoid dendritic cells and B cells. Here we show that HMGB1, a nuclear DNA-binding protein released from necrotic cells, was an essential component of DNA-containing immune complexes that stimulated cytokine production through a TLR9-MyD88 pathway involving the multivalent receptor RAGE. Moreover, binding of HMGB1 to class A CpG oligodeoxynucleotides considerably augmented cytokine production by means of TLR9 and RAGE. Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis.
- Boston College United States
- University of Massachusetts Medical School United States
- MedImmune United States
- Heidelberg University Germany
- Boston University United States
B-Lymphocytes, Receptor for Advanced Glycation End Products, 610, Receptors, Cell Surface, Antigen-Antibody Complex, Dendritic Cells, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Oligodeoxyribonucleotides, Toll-Like Receptor 9, Animals, Lupus Erythematosus, Systemic, CpG Islands, HMGB1 Protein
B-Lymphocytes, Receptor for Advanced Glycation End Products, 610, Receptors, Cell Surface, Antigen-Antibody Complex, Dendritic Cells, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Oligodeoxyribonucleotides, Toll-Like Receptor 9, Animals, Lupus Erythematosus, Systemic, CpG Islands, HMGB1 Protein
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