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Nat Immunol. 2007 May;8(5):487-96. Epub 2007 Apr 8.

Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE.

Author information

  • 1Inflammation and Autoimmune Group, Research Department, MedImmune, Gaithersburg, Maryland 20878, USA.

Erratum in

  • Nat Immunol. 2007 Jul;8(7):780.

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.

Comment in

PMID:
17417641
[PubMed - indexed for MEDLINE]
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