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Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis

BACKGROUND: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS: To generate expression...

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Autores principales: Andersson, Sofia E. M., Eneljung, Tove, Tengvall, Sara, Jirholt, Pernilla, Stern, Anna, Henningsson, Louise, Liang, Bibo, Thorarinsdottir, Katrin, Kihlberg, Jan, Holmdahl, Rikard, Mårtensson, Inga-Lill, Gustafsson, Kenth, Gjertsson, Inger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908726/
https://www.ncbi.nlm.nih.gov/pubmed/27301320
http://dx.doi.org/10.1186/s13075-016-1037-7
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author Andersson, Sofia E. M.
Eneljung, Tove
Tengvall, Sara
Jirholt, Pernilla
Stern, Anna
Henningsson, Louise
Liang, Bibo
Thorarinsdottir, Katrin
Kihlberg, Jan
Holmdahl, Rikard
Mårtensson, Inga-Lill
Gustafsson, Kenth
Gjertsson, Inger
author_facet Andersson, Sofia E. M.
Eneljung, Tove
Tengvall, Sara
Jirholt, Pernilla
Stern, Anna
Henningsson, Louise
Liang, Bibo
Thorarinsdottir, Katrin
Kihlberg, Jan
Holmdahl, Rikard
Mårtensson, Inga-Lill
Gustafsson, Kenth
Gjertsson, Inger
author_sort Andersson, Sofia E. M.
collection PubMed
description BACKGROUND: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. RESULTS: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naïve mice ameliorated the development of CII-induced arthritis. CONCLUSION: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-1037-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-49087262016-06-16 Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis Andersson, Sofia E. M. Eneljung, Tove Tengvall, Sara Jirholt, Pernilla Stern, Anna Henningsson, Louise Liang, Bibo Thorarinsdottir, Katrin Kihlberg, Jan Holmdahl, Rikard Mårtensson, Inga-Lill Gustafsson, Kenth Gjertsson, Inger Arthritis Res Ther Research Article BACKGROUND: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. RESULTS: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naïve mice ameliorated the development of CII-induced arthritis. CONCLUSION: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-1037-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-14 2016 /pmc/articles/PMC4908726/ /pubmed/27301320 http://dx.doi.org/10.1186/s13075-016-1037-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Andersson, Sofia E. M.
Eneljung, Tove
Tengvall, Sara
Jirholt, Pernilla
Stern, Anna
Henningsson, Louise
Liang, Bibo
Thorarinsdottir, Katrin
Kihlberg, Jan
Holmdahl, Rikard
Mårtensson, Inga-Lill
Gustafsson, Kenth
Gjertsson, Inger
Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title_full Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title_fullStr Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title_full_unstemmed Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title_short Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
title_sort collagen epitope expression on b cells is sufficient to confer tolerance to collagen-induced arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908726/
https://www.ncbi.nlm.nih.gov/pubmed/27301320
http://dx.doi.org/10.1186/s13075-016-1037-7
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