Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers
Autor: | David D. Brand, Amanda Gamboa, Indra Sandal, Edward F. Rosloniec, Jiwen Luo, Anastasios Karydis, Amanda Prislovsky |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Knees
Alveolar Bone Loss Arthritis Knee Joints Biochemistry Arthritis Rheumatoid Epitopes Mice Skeletal Joints Medicine and Health Sciences Enzyme-Linked Immunoassays Musculoskeletal System Immune Response Multidisciplinary biology Animal Models Phenotype Phenotypes Experimental Organism Systems Rheumatoid arthritis Legs Medicine Anatomy Porphyromonas gingivalis Research Article Transgene Science Immunology Mouse Models Rheumatoid Arthritis Context (language use) Research and Analysis Methods Autoimmune Diseases Periodontal pathogen Model Organisms Immune system Rheumatology Genetics medicine Animals Humans Immunoassays Skeleton Correction Biology and Life Sciences Proteins medicine.disease biology.organism_classification Arthritis Experimental Body Limbs Immunologic Techniques Animal Studies Clinical Immunology Clinical Medicine Collagens Biomarkers |
Zdroj: | PLoS ONE, Vol 16, Iss 4, p e0250177 (2021) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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