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Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation
Chemokines control the migratory patterns and positioning of immune cells to organize immune responses to pathogens. However, many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signatures. We report that a series of chemokines, including CXCL4, CXCL10, CXCL1...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161158/ https://www.ncbi.nlm.nih.gov/pubmed/35640018 http://dx.doi.org/10.1084/jem.20212142 |
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author | Du, Yong Ah Kioon, Marie Dominique Laurent, Paoline Chaudhary, Vidyanath Pierides, Michael Yang, Chao Oliver, David Ivashkiv, Lionel B. Barrat, Franck J. |
author_facet | Du, Yong Ah Kioon, Marie Dominique Laurent, Paoline Chaudhary, Vidyanath Pierides, Michael Yang, Chao Oliver, David Ivashkiv, Lionel B. Barrat, Franck J. |
author_sort | Du, Yong |
collection | PubMed |
description | Chemokines control the migratory patterns and positioning of immune cells to organize immune responses to pathogens. However, many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signatures. We report that a series of chemokines, including CXCL4, CXCL10, CXCL12, and CCL5, can superinduce type I IFN (IFN-I) by TLR9-activated plasmacytoid DCs (pDCs), independently of their respective known chemokine receptors. Mechanistically, we show that chemokines such as CXCL4 mediate transcriptional and epigenetic changes in pDCs, mostly targeted to the IFN-I pathways. We describe that chemokines physically interact with DNA to form nanoparticles that promote clathrin-mediated cellular uptake and delivery of DNA in the early endosomes of pDCs. Using two separate mouse models of skin inflammation, we observed the presence of CXCL4 associated with DNA in vivo. These data reveal a noncanonical role for chemokines to serve as nucleic acid delivery vectors to modulate TLR signaling, with implications for the chronic presence of IFN-I by pDCs in autoimmune diseases. |
format | Online Article Text |
id | pubmed-9161158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91611582022-11-30 Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation Du, Yong Ah Kioon, Marie Dominique Laurent, Paoline Chaudhary, Vidyanath Pierides, Michael Yang, Chao Oliver, David Ivashkiv, Lionel B. Barrat, Franck J. J Exp Med Article Chemokines control the migratory patterns and positioning of immune cells to organize immune responses to pathogens. However, many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signatures. We report that a series of chemokines, including CXCL4, CXCL10, CXCL12, and CCL5, can superinduce type I IFN (IFN-I) by TLR9-activated plasmacytoid DCs (pDCs), independently of their respective known chemokine receptors. Mechanistically, we show that chemokines such as CXCL4 mediate transcriptional and epigenetic changes in pDCs, mostly targeted to the IFN-I pathways. We describe that chemokines physically interact with DNA to form nanoparticles that promote clathrin-mediated cellular uptake and delivery of DNA in the early endosomes of pDCs. Using two separate mouse models of skin inflammation, we observed the presence of CXCL4 associated with DNA in vivo. These data reveal a noncanonical role for chemokines to serve as nucleic acid delivery vectors to modulate TLR signaling, with implications for the chronic presence of IFN-I by pDCs in autoimmune diseases. Rockefeller University Press 2022-05-31 /pmc/articles/PMC9161158/ /pubmed/35640018 http://dx.doi.org/10.1084/jem.20212142 Text en © 2022 Du et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Du, Yong Ah Kioon, Marie Dominique Laurent, Paoline Chaudhary, Vidyanath Pierides, Michael Yang, Chao Oliver, David Ivashkiv, Lionel B. Barrat, Franck J. Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title | Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title_full | Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title_fullStr | Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title_full_unstemmed | Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title_short | Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation |
title_sort | chemokines form nanoparticles with dna and can superinduce tlr-driven immune inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161158/ https://www.ncbi.nlm.nih.gov/pubmed/35640018 http://dx.doi.org/10.1084/jem.20212142 |
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