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Siglec-H protects from virus-triggered severe systemic autoimmunity
It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced b...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986536/ https://www.ncbi.nlm.nih.gov/pubmed/27377589 http://dx.doi.org/10.1084/jem.20160189 |
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author | Schmitt, Heike Sell, Sabrina Koch, Julia Seefried, Martina Sonnewald, Sophia Daniel, Christoph Winkler, Thomas H. Nitschke, Lars |
author_facet | Schmitt, Heike Sell, Sabrina Koch, Julia Seefried, Martina Sonnewald, Sophia Daniel, Christoph Winkler, Thomas H. Nitschke, Lars |
author_sort | Schmitt, Heike |
collection | PubMed |
description | It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec-H–deficient pDCs produce more of the type I IFN, IFN-α, in vitro and that Siglec-H knockout (KO) mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus–like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. |
format | Online Article Text |
id | pubmed-4986536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49865362017-01-25 Siglec-H protects from virus-triggered severe systemic autoimmunity Schmitt, Heike Sell, Sabrina Koch, Julia Seefried, Martina Sonnewald, Sophia Daniel, Christoph Winkler, Thomas H. Nitschke, Lars J Exp Med Research Articles It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec-H–deficient pDCs produce more of the type I IFN, IFN-α, in vitro and that Siglec-H knockout (KO) mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus–like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. The Rockefeller University Press 2016-07-25 /pmc/articles/PMC4986536/ /pubmed/27377589 http://dx.doi.org/10.1084/jem.20160189 Text en © 2016 Schmitt 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 | Research Articles Schmitt, Heike Sell, Sabrina Koch, Julia Seefried, Martina Sonnewald, Sophia Daniel, Christoph Winkler, Thomas H. Nitschke, Lars Siglec-H protects from virus-triggered severe systemic autoimmunity |
title | Siglec-H protects from virus-triggered severe systemic autoimmunity |
title_full | Siglec-H protects from virus-triggered severe systemic autoimmunity |
title_fullStr | Siglec-H protects from virus-triggered severe systemic autoimmunity |
title_full_unstemmed | Siglec-H protects from virus-triggered severe systemic autoimmunity |
title_short | Siglec-H protects from virus-triggered severe systemic autoimmunity |
title_sort | siglec-h protects from virus-triggered severe systemic autoimmunity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986536/ https://www.ncbi.nlm.nih.gov/pubmed/27377589 http://dx.doi.org/10.1084/jem.20160189 |
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