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RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA
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 mec...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804942/ https://www.ncbi.nlm.nih.gov/pubmed/24081950 http://dx.doi.org/10.1084/jem.20120201 |
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author | 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 |
author_facet | 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 |
author_sort | Sirois, Cherilyn M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3804942 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38049422014-04-21 RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA 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 J Exp Med Article 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. The Rockefeller University Press 2013-10-21 /pmc/articles/PMC3804942/ /pubmed/24081950 http://dx.doi.org/10.1084/jem.20120201 Text en © 2013 Sirois et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article 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 RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title | RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title_full | RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title_fullStr | RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title_full_unstemmed | RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title_short | RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA |
title_sort | rage is a nucleic acid receptor that promotes inflammatory responses to dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804942/ https://www.ncbi.nlm.nih.gov/pubmed/24081950 http://dx.doi.org/10.1084/jem.20120201 |
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