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RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

Authors :
Sirois, Cherilyn M.
Jin, Tengchuan
Miller, Allison L.
Bertheloot, Damien
Nakamura, Hirotaka
Horvath, Gabor L.
Mian, Abubakar
Jiang, Jiansheng
Schrum, Jacob
Bossaller, Lukas
Pelka, Karin
Garbi, Natalio
Brewah, Yambasu
Tian, Jane
Chang, ChewShun
Chowdhury, Partha S.
Sims, Gary P.
Kolbeck, Roland
Coyle, Anthony J.
Humbles, Alison A.
Xiao, T. Sam
Latz, Eicke
Source :
The Journal of Experimental Medicine; October 2013, Vol. 210 Issue: 11 p2447-2463, 17p
Publication Year :
2013

Abstract

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 RAGEā€“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.

Details

Language :
English
ISSN :
00221007 and 15409538
Volume :
210
Issue :
11
Database :
Supplemental Index
Journal :
The Journal of Experimental Medicine
Publication Type :
Periodical
Accession number :
ejs31303799
Full Text :
https://doi.org/10.1084/jem.20120201