PMID- 27784339 OWN - NLM STAT- MEDLINE DCOM- 20171107 LR - 20210507 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 18 IP - 1 DP - 2016 Oct 26 TI - Bone loss and aggravated autoimmune arthritis in HLA-DRbeta1-bearing humanized mice following oral challenge with Porphyromonas gingivalis. PG - 249 LID - 249 AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FAU - Sandal, Indra AU - Sandal I AD - Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. FAU - Karydis, Anastasios AU - Karydis A AD - Department of Periodontology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. FAU - Luo, Jiwen AU - Luo J AD - Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. FAU - Prislovsky, Amanda AU - Prislovsky A AD - Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. FAU - Whittington, Karen B AU - Whittington KB AD - Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. FAU - Rosloniec, Edward F AU - Rosloniec EF AD - Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. AD - Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. AD - Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. FAU - Dong, Chen AU - Dong C AD - Institute for Immunology, Tsinghua University, Beijing, 100084, China. FAU - Novack, Deborah V AU - Novack DV AD - Musculoskeletal Research Center, Departments of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO, 63110, USA. FAU - Mydel, Piotr AU - Mydel P AD - Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway. FAU - Zheng, Song Guo AU - Zheng SG AD - Division of Rheumatology, Department of Medicine, Pennsylvania State University Hershey College of Medicine, Hershey, PA, 17033, USA. FAU - Radic, Marko Z AU - Radic MZ AD - Department of Microbiology Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. FAU - Brand, David D AU - Brand DD AUID- ORCID: 0000-0002-9260-7963 AD - Research Service, Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. David.Brand@va.gov. AD - Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. David.Brand@va.gov. AD - Department of Microbiology Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. David.Brand@va.gov. LA - eng GR - I01 BX001193/BX/BLRD VA/United States GR - R01 AR059103/AR/NIAMS NIH HHS/United States GR - P30 AR057235/AR/NIAMS NIH HHS/United States GR - I01 BX003256/BX/BLRD VA/United States GR - I01 BX001045/BX/BLRD VA/United States GR - IP1 BX001607/BX/BLRD VA/United States GR - I01 BX003487/BX/BLRD VA/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20161026 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (HLA-DRB1 Chains) SB - IM MH - Alveolar Bone Loss/microbiology/pathology MH - Animals MH - Arthritis, Experimental/*immunology/microbiology MH - Arthritis, Rheumatoid/*immunology/microbiology MH - Bacteroidaceae Infections/complications/*immunology MH - Enzyme-Linked Immunosorbent Assay MH - Femur/pathology MH - Flow Cytometry MH - HLA-DRB1 Chains MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Periodontitis/complications/*immunology MH - Porphyromonas gingivalis MH - X-Ray Microtomography PMC - PMC5081677 OTO - NOTNLM OT - Animal model OT - Periodontal disease OT - Porphyromonas gingivalis OT - Rheumatoid arthritis EDAT- 2016/10/28 06:00 MHDA- 2017/11/08 06:00 PMCR- 2016/10/26 CRDT- 2016/10/28 06:00 PHST- 2016/06/14 00:00 [received] PHST- 2016/09/30 00:00 [accepted] PHST- 2016/10/28 06:00 [pubmed] PHST- 2017/11/08 06:00 [medline] PHST- 2016/10/28 06:00 [entrez] PHST- 2016/10/26 00:00 [pmc-release] AID - 10.1186/s13075-016-1143-6 [pii] AID - 1143 [pii] AID - 10.1186/s13075-016-1143-6 [doi] PST - epublish SO - Arthritis Res Ther. 2016 Oct 26;18(1):249. doi: 10.1186/s13075-016-1143-6.