Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Interdisciplinary Graduate Program
Department of Medicine, Division of Infectious Diseases and Immunology
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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
Nature Immunology 8, 487 - 496 (2007). doi:10.1038/ni1457
Tian J, Avalos AM, Mao S, Chen B, Senthil K, Wu H, Parroche P, Drabic S, Golenbock DT, Sirois CM, Hua J, An L, Audoly L, La Rosa G, Bierhaus A, Naworth P, Marshak-Rothstein A, Crow MK, Fitzgerald KA, Latz E, Kiener PA, Coyle AJ. (2007). Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. GSBS Student Publications. https://doi.org/10.1038/ni1457. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1652