GSBS Student Publications

Title

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

Student Author(s)

Cherilyn M. Sirois

GSBS Program

Interdisciplinary Graduate Program

Publication Date

2007-05-01

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Document Type

Article

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences

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.

DOI of Published Version

10.1038/ni1457

Source

Nature Immunology 8, 487 - 496 (2007). doi:10.1038/ni1457

Journal/Book/Conference Title

Nature immunology

Related Resources

Link to article in PubMed

PubMed ID

17417641

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