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RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement

Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837–847) established the unique capacity...

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Autores principales: Lau, Christina M., Broughton, Courtney, Tabor, Abigail S., Akira, Shizuo, Flavell, Richard A., Mamula, Mark J., Christensen, Sean R., Shlomchik, Mark J., Viglianti, Gregory A., Rifkin, Ian R., Marshak-Rothstein, Ann
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213226/
https://www.ncbi.nlm.nih.gov/pubmed/16260486
http://dx.doi.org/10.1084/jem.20050630
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author Lau, Christina M.
Broughton, Courtney
Tabor, Abigail S.
Akira, Shizuo
Flavell, Richard A.
Mamula, Mark J.
Christensen, Sean R.
Shlomchik, Mark J.
Viglianti, Gregory A.
Rifkin, Ian R.
Marshak-Rothstein, Ann
author_facet Lau, Christina M.
Broughton, Courtney
Tabor, Abigail S.
Akira, Shizuo
Flavell, Richard A.
Mamula, Mark J.
Christensen, Sean R.
Shlomchik, Mark J.
Viglianti, Gregory A.
Rifkin, Ian R.
Marshak-Rothstein, Ann
author_sort Lau, Christina M.
collection PubMed
description Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837–847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-α, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.
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spelling pubmed-22132262008-03-11 RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement Lau, Christina M. Broughton, Courtney Tabor, Abigail S. Akira, Shizuo Flavell, Richard A. Mamula, Mark J. Christensen, Sean R. Shlomchik, Mark J. Viglianti, Gregory A. Rifkin, Ian R. Marshak-Rothstein, Ann J Exp Med Brief Definitive Report Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837–847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-α, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers. The Rockefeller University Press 2005-11-07 /pmc/articles/PMC2213226/ /pubmed/16260486 http://dx.doi.org/10.1084/jem.20050630 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 Brief Definitive Report
Lau, Christina M.
Broughton, Courtney
Tabor, Abigail S.
Akira, Shizuo
Flavell, Richard A.
Mamula, Mark J.
Christensen, Sean R.
Shlomchik, Mark J.
Viglianti, Gregory A.
Rifkin, Ian R.
Marshak-Rothstein, Ann
RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title_full RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title_fullStr RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title_full_unstemmed RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title_short RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
title_sort rna-associated autoantigens activate b cells by combined b cell antigen receptor/toll-like receptor 7 engagement
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213226/
https://www.ncbi.nlm.nih.gov/pubmed/16260486
http://dx.doi.org/10.1084/jem.20050630
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