We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE.
- Authors
Tian, Jane; Avalos, Ana Maria; Mao, Su-Yau; Chen, Bo; Senthil, Kannaki; Wu, Herren; Parroche, Peggy; Drabic, Stacey; Golenbock, Douglas; Sirois, Cherilyn; Hua, Jing; An, Ling Ling; Audoly, Laurent; La Rosa, Greg; Bierhaus, Angelika; Naworth, Peter; Marshak-Rothstein, Ann; Crow, Mary K; Fitzgerald, Katherine A; Latz, Eicke; Kiener, Peter A; Coyle, Anthony J
- Abstract
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.
- Publication
Nature immunology, 2007, Vol 8, Issue 5, p487
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1457