1. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA
- Author
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Jiansheng Jiang, Tengchuan Jin, Chew-Shun Chang, T. Sam Xiao, Hirotaka Nakamura, Cherilyn M. Sirois, Gary P. Sims, Damien Bertheloot, Alison A. Humbles, Karin Pelka, Jane Tian, Anthony J. Coyle, Abubakar Mian, Eicke Latz, Jacob E. Schrum, Roland Kolbeck, Yambasu A. Brewah, Allison L. Miller, Gabor Horvath, Partha S. Chowdhury, Lukas Bossaller, and Natalio Garbi
- Subjects
Models, Molecular ,Letter ,endocrine system diseases ,Receptor for Advanced Glycation End Products ,Immune receptor ,Crystallography, X-Ray ,Ligands ,RAGE (receptor) ,chemistry.chemical_compound ,Mice ,Immunology and Allergy ,Receptors, Immunologic ,Receptor ,Lung ,chemistry [DNA] ,pathology [Lung] ,NF-kappa B ,metabolism [Receptors, Immunologic] ,metabolism [Toll-Like Receptor 9] ,pathology [Pneumonia] ,Endocytosis ,Biochemistry ,chemistry [Receptors, Immunologic] ,cardiovascular system ,metabolism [NF-kappa B] ,Protein Binding ,metabolism [Endosomes] ,metabolism [Pneumonia] ,Immunology ,Static Electricity ,chemical and pharmacologic phenomena ,Endosomes ,Biology ,metabolism [Lung] ,metabolism [Cell Membrane] ,Article ,Immune system ,Animals ,Humans ,ddc:610 ,Base Sequence ,Cell Membrane ,Correction ,RNA ,nutritional and metabolic diseases ,Cell Biology ,DNA ,Pneumonia ,Molecular biology ,Toll-Like Receptor 9 ,Protein Structure, Tertiary ,Mice, Inbred C57BL ,HEK293 Cells ,chemistry ,Nucleic acid ,metabolism [DNA] ,Protein Multimerization ,human activities ,HeLa Cells - Abstract
Receptor for advanced glycation end-products (RAGE) detects nucleic acids and promotes DNA uptake into endosomes, which in turn lowers the immune recognition threshold for TLR9 activation., Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis of RAGE–DNA complexes indicated that DNA interacted with dimers of the outermost RAGE extracellular domains, and could induce formation of higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable to mount a typical inflammatory response to DNA in the lung, indicating that RAGE is important for the detection of nucleic acids in vivo.
- Published
- 2013
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