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Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8
Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid–recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the an...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737167/ https://www.ncbi.nlm.nih.gov/pubmed/19703986 http://dx.doi.org/10.1084/jem.20090480 |
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author | Ganguly, Dipyaman Chamilos, Georgios Lande, Roberto Gregorio, Josh Meller, Stephan Facchinetti, Valeria Homey, Bernhard Barrat, Franck J. Zal, Tomasz Gilliet, Michel |
author_facet | Ganguly, Dipyaman Chamilos, Georgios Lande, Roberto Gregorio, Josh Meller, Stephan Facchinetti, Valeria Homey, Bernhard Barrat, Franck J. Zal, Tomasz Gilliet, Michel |
author_sort | Ganguly, Dipyaman |
collection | PubMed |
description | Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid–recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA–LL37 complexes activate TLR7 and, like self-DNA–LL37 complexes, trigger the secretion of IFN-α without inducing maturation or the production of IL-6 and TNF-α. In contrast to self-DNA–LL37 complexes, self-RNA–LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-α and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA–LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis. |
format | Text |
id | pubmed-2737167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27371672010-02-28 Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 Ganguly, Dipyaman Chamilos, Georgios Lande, Roberto Gregorio, Josh Meller, Stephan Facchinetti, Valeria Homey, Bernhard Barrat, Franck J. Zal, Tomasz Gilliet, Michel J Exp Med Article Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid–recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA–LL37 complexes activate TLR7 and, like self-DNA–LL37 complexes, trigger the secretion of IFN-α without inducing maturation or the production of IL-6 and TNF-α. In contrast to self-DNA–LL37 complexes, self-RNA–LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-α and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA–LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis. The Rockefeller University Press 2009-08-31 /pmc/articles/PMC2737167/ /pubmed/19703986 http://dx.doi.org/10.1084/jem.20090480 Text en © 2009 Ganguly 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.jem.org/misc/terms.shtml). 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 Ganguly, Dipyaman Chamilos, Georgios Lande, Roberto Gregorio, Josh Meller, Stephan Facchinetti, Valeria Homey, Bernhard Barrat, Franck J. Zal, Tomasz Gilliet, Michel Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title | Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title_full | Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title_fullStr | Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title_full_unstemmed | Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title_short | Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 |
title_sort | self-rna–antimicrobial peptide complexes activate human dendritic cells through tlr7 and tlr8 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737167/ https://www.ncbi.nlm.nih.gov/pubmed/19703986 http://dx.doi.org/10.1084/jem.20090480 |
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