title: Mucosal Langerhans Cells Promote Differentiation of Th17 Cells in a Murine Model of Periodontitis but Are Not Required for Porphyromonas gingivalis-Driven Alveolar Bone Destruction.
abstract: Periodontitis is a chronic oral inflammatory disease affecting one in five individuals that can lead to tooth loss. CD4(+) Th cells activated by a microbial biofilm are thought to contribute to the destruction of alveolar bone surrounding teeth by influencing osteoclastogenesis through IL-17A and receptor activator for NF-κB ligand effects. The relative roles of mucosal Ag presentation cells in directing Th cell immune responses against oral pathogens and their contribution to destruction of alveolar bone remain unknown. We tested the contribution of mucosal Langerhans cells (LCs) to alveolar bone homeostasis in mice following oral colonization with a well-characterized human periodontal pathogen, Porphyromonas gingivalis We found that oral mucosal LCs did not protect from or exacerbate crestal alveolar bone destruction but were responsible for promoting differentiation of Th17 cells specific to P. gingivalis. In mice lacking LCs the Th17 response was suppressed and a Th1 response predominated. Bypassing LCs with systemic immunization of P. gingivalis resulted in a predominantly P. gingivalis-specific Th1 response regardless of whether LCs were present. Interestingly, we find that in vivo clonal expansion of P. gingivalis-specific Th cells and induced regulatory T cells does not depend on mucosal LCs. Furthermore, destruction of crestal alveolar bone induced by P. gingivalis colonization occurred regardless of the presence of mucosal LCs or P. gingivalis-specific Th17 cells. Our data indicate that both LCs and Th17 cells are redundant in contributing to alveolar bone destruction in a murine model of periodontitis.
authors.affiliation: Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis MN 55455; and.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Bittner-Eddy
authors.affiliation: Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis MN 55455; and.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Fischer
authors.affiliation: Department of Dermatology, Medical School, University of Minnesota, Minneapolis MN 55455.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.affiliation: Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis MN 55455; and.
authors.forename: Kathleen
authors.identifier: 0000-0003-1524-8394
authors.initials: K
authors.lastname: Thieu
authors.affiliation: Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis MN 55455; and costa002@umn.edu.
authors.forename: Massimo
authors.identifier: 0000-0001-5922-3709
authors.initials: M
authors.lastname: Costalonga
mesh_terms: D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009061:Mouth Mucosa / Q000276:immunology* / Q000382:microbiology; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D016966:Porphyromonas gingivalis; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*