title: Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis.
abstract: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies.
  
  
  
  To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production.
  
  
  
  Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice.
  
  
  
  Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present.
authors: Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.
authors: Indra
authors: I
authors: Sandal
authors: Department of Periodontology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors: Anastasios
authors: A
authors: Karydis
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors: Jiwen
authors: J
authors: Luo
authors: Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.
authors: Amanda
authors: A
authors: Prislovsky
authors: Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.
authors: Karen B
authors: KB
authors: Whittington
authors: Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.|Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.|Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors: Edward F
authors: EF
authors: Rosloniec
authors: Institute for Immunology, Tsinghua University, Beijing, 100084, China.
authors: Chen
authors: C
authors: Dong
authors: Musculoskeletal Research Center, Departments of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors: Deborah V
authors: DV
authors: Novack
authors: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Piotr
authors: P
authors: Mydel
authors: Division of Rheumatology, Department of Medicine, Pennsylvania State University Hershey College of Medicine, Hershey, PA, 17033, USA.
authors: Song Guo
authors: SG
authors: Zheng
authors: Department of Microbiology Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors: Marko Z
authors: MZ
authors: Radic
authors: Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. David.Brand@va.gov.|Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. David.Brand@va.gov.|Department of Microbiology Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. David.Brand@va.gov.
authors: David D
authors: 0000-0002-9260-7963
authors: DD
authors: Brand
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000382:microbiology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D016866:Bacteroidaceae Infections / Q000150:complications / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005269:Femur / Q000473:pathology; D005434:Flow Cytometry; D059811:HLA-DRB1 Chains; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010518:Periodontitis / Q000150:complications / Q000276:immunology*; D016966:Porphyromonas gingivalis; D055114:X-Ray Microtomography
chemical_list: D059811:HLA-DRB1 Chains
keywords: Animal model; Periodontal disease; Porphyromonas gingivalis; Rheumatoid arthritis