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Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to certain cellular macromolecules, such as the small nuclear ribonucleoprotein particles (snRNPs), which had been considered to be passive targets of the autoimmune response. SLE is also ch...

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Autores principales: Vollmer, Jörg, Tluk, Sibylle, Schmitz, Claudia, Hamm, Svetlana, Jurk, Marion, Forsbach, Alexandra, Akira, Shizuo, Kelly, Kindra M., Reeves, Westley H., Bauer, Stefan, Krieg, Arthur M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213330/
https://www.ncbi.nlm.nih.gov/pubmed/16330816
http://dx.doi.org/10.1084/jem.20051696
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author Vollmer, Jörg
Tluk, Sibylle
Schmitz, Claudia
Hamm, Svetlana
Jurk, Marion
Forsbach, Alexandra
Akira, Shizuo
Kelly, Kindra M.
Reeves, Westley H.
Bauer, Stefan
Krieg, Arthur M.
author_facet Vollmer, Jörg
Tluk, Sibylle
Schmitz, Claudia
Hamm, Svetlana
Jurk, Marion
Forsbach, Alexandra
Akira, Shizuo
Kelly, Kindra M.
Reeves, Westley H.
Bauer, Stefan
Krieg, Arthur M.
author_sort Vollmer, Jörg
collection PubMed
description Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to certain cellular macromolecules, such as the small nuclear ribonucleoprotein particles (snRNPs), which had been considered to be passive targets of the autoimmune response. SLE is also characterized by the increased expression of type I interferon (IFN), which appears to be associated with the development and severity of disease. Here, we show that specific, highly conserved RNA sequences within snRNPs can stimulate Toll-like receptors (TLRs) 7 and 8 as well as activate innate immune cells, such as plasmacytoid dendritic cells (pDCs), which respond by secreting high levels of type I IFN. SLE patient sera containing autoantibodies to snRNPs form immune complexes that are taken up through the Fc receptor γRII and efficiently stimulate pDCs to secrete type I IFNs. These results demonstrate that a prototype autoantigen, the snRNP, can directly stimulate innate immunity and suggest that autoantibodies against snRNP may initiate SLE by stimulating TLR7/8.
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spelling pubmed-22133302008-03-11 Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8 Vollmer, Jörg Tluk, Sibylle Schmitz, Claudia Hamm, Svetlana Jurk, Marion Forsbach, Alexandra Akira, Shizuo Kelly, Kindra M. Reeves, Westley H. Bauer, Stefan Krieg, Arthur M. J Exp Med Article Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to certain cellular macromolecules, such as the small nuclear ribonucleoprotein particles (snRNPs), which had been considered to be passive targets of the autoimmune response. SLE is also characterized by the increased expression of type I interferon (IFN), which appears to be associated with the development and severity of disease. Here, we show that specific, highly conserved RNA sequences within snRNPs can stimulate Toll-like receptors (TLRs) 7 and 8 as well as activate innate immune cells, such as plasmacytoid dendritic cells (pDCs), which respond by secreting high levels of type I IFN. SLE patient sera containing autoantibodies to snRNPs form immune complexes that are taken up through the Fc receptor γRII and efficiently stimulate pDCs to secrete type I IFNs. These results demonstrate that a prototype autoantigen, the snRNP, can directly stimulate innate immunity and suggest that autoantibodies against snRNP may initiate SLE by stimulating TLR7/8. The Rockefeller University Press 2005-12-05 /pmc/articles/PMC2213330/ /pubmed/16330816 http://dx.doi.org/10.1084/jem.20051696 Text en Copyright © 2005, The Rockefeller University Press 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 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Vollmer, Jörg
Tluk, Sibylle
Schmitz, Claudia
Hamm, Svetlana
Jurk, Marion
Forsbach, Alexandra
Akira, Shizuo
Kelly, Kindra M.
Reeves, Westley H.
Bauer, Stefan
Krieg, Arthur M.
Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title_full Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title_fullStr Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title_full_unstemmed Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title_short Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
title_sort immune stimulation mediated by autoantigen binding sites within small nuclear rnas involves toll-like receptors 7 and 8
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213330/
https://www.ncbi.nlm.nih.gov/pubmed/16330816
http://dx.doi.org/10.1084/jem.20051696
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