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Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers

Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim o...

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Autores principales: Karydis, Anastasios, Sandal, Indra, Luo, Jiwen, Prislovsky, Amanda, Gamboa, Amanda, Rosloniec, Edward F., Brand, David D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049293/
https://www.ncbi.nlm.nih.gov/pubmed/33857232
http://dx.doi.org/10.1371/journal.pone.0250177
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author Karydis, Anastasios
Sandal, Indra
Luo, Jiwen
Prislovsky, Amanda
Gamboa, Amanda
Rosloniec, Edward F.
Brand, David D.
author_facet Karydis, Anastasios
Sandal, Indra
Luo, Jiwen
Prislovsky, Amanda
Gamboa, Amanda
Rosloniec, Edward F.
Brand, David D.
author_sort Karydis, Anastasios
collection PubMed
description Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity.
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spelling pubmed-80492932021-04-21 Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers Karydis, Anastasios Sandal, Indra Luo, Jiwen Prislovsky, Amanda Gamboa, Amanda Rosloniec, Edward F. Brand, David D. PLoS One Research Article Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity. Public Library of Science 2021-04-15 /pmc/articles/PMC8049293/ /pubmed/33857232 http://dx.doi.org/10.1371/journal.pone.0250177 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Karydis, Anastasios
Sandal, Indra
Luo, Jiwen
Prislovsky, Amanda
Gamboa, Amanda
Rosloniec, Edward F.
Brand, David D.
Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title_full Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title_fullStr Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title_full_unstemmed Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title_short Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
title_sort influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049293/
https://www.ncbi.nlm.nih.gov/pubmed/33857232
http://dx.doi.org/10.1371/journal.pone.0250177
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