TY  - JOUR
AU  - Sirois, Cherilyn M
AU  - Jin, Tengchuan
AU  - Miller, Allison L
AU  - Bertheloot, Damien
AU  - Nakamura, Hirotaka
AU  - Horvath, Gabor L
AU  - Mian, Abubakar
AU  - Jiang, Jiansheng
AU  - Schrum, Jacob
AU  - Bossaller, Lukas
AU  - Pelka, Karin
AU  - Garbi, Natalio
AU  - Brewah, Yambasu
AU  - Tian, Jane
AU  - Chang, ChewShun
AU  - Chowdhury, Partha S
AU  - Sims, Gary P
AU  - Kolbeck, Roland
AU  - Coyle, Anthony J
AU  - Humbles, Alison A
AU  - Xiao, T Sam
AU  - Latz, Eicke
TI  - RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.
JO  - Journal of experimental medicine
VL  - 210
IS  - 11
SN  - 1540-9538
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DZNE-2020-03408
SP  - 2447-2463
PY  - 2013
AB  - 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.
KW  - Animals
KW  - Base Sequence
KW  - Cell Membrane: metabolism
KW  - Crystallography, X-Ray
KW  - DNA: chemistry
KW  - DNA: metabolism
KW  - Endocytosis
KW  - Endosomes: metabolism
KW  - HEK293 Cells
KW  - HeLa Cells
KW  - Humans
KW  - Ligands
KW  - Lung: metabolism
KW  - Lung: pathology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Models, Molecular
KW  - NF-kappa B: metabolism
KW  - Pneumonia: metabolism
KW  - Pneumonia: pathology
KW  - Protein Binding
KW  - Protein Multimerization
KW  - Protein Structure, Tertiary
KW  - Receptor for Advanced Glycation End Products
KW  - Receptors, Immunologic: chemistry
KW  - Receptors, Immunologic: metabolism
KW  - Static Electricity
KW  - Toll-Like Receptor 9: metabolism
KW  - Ligands (NLM Chemicals)
KW  - NF-kappa B (NLM Chemicals)
KW  - Receptor for Advanced Glycation End Products (NLM Chemicals)
KW  - Receptors, Immunologic (NLM Chemicals)
KW  - Toll-Like Receptor 9 (NLM Chemicals)
KW  - DNA (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24081950
C2  - pmc:PMC3804942
DO  - DOI:10.1084/jem.20120201
UR  - https://pub.dzne.de/record/137086
ER  -