B and T Lymphocytes Are the Primary Sources of RANKL in the Bone Resorptive Lesion of Periodontal Disease

Kawai, Toshihisa; Matsuyama, Takashi; Hosokawa, Yoshitaka; Makihira, Seicho; Seki, Makoto; Karimbux, Nadeem Y.; Gonçalves, Reginaldo Bruno; Valverde, Paloma; Dibart, Serge; Li, Yi Ping; Miranda, Letícia Algarves; Ernst, Cory W.O.; Izumi, Yuichi; Taubman, Martin A.

doi:10.2353/ajpath.2006.060180

Cited by 466 publications

(537 citation statements)

References 57 publications

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“…Recently, it has been shown that most CD20 + B cells in periodontitis lesions express RANKL (61). However, it is unclear whether those cells are plasma cells or memory B cells.…”

Section: Discussionmentioning

confidence: 99%

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Mahanonda

Champaiboon

Subbalekha

et al. 2016

The Journal of Immunology

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The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19+CD27+CD38− memory B cells, the major B cell component in periodontitis was CD19+CD27+CD38+CD138+HLA-DRlow plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell–activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis.

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“…Recently, it has been shown that most CD20 + B cells in periodontitis lesions express RANKL (61). However, it is unclear whether those cells are plasma cells or memory B cells.…”

Section: Discussionmentioning

confidence: 99%

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Mahanonda

Champaiboon

Subbalekha

et al. 2016

The Journal of Immunology

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“…51) or are predominantly pathogenic/destructive (52,53). Activated T cells express receptor activator of NF-B ligand (RANKL), which stimulates osteoclast differentiation and bone resorption, and elevated numbers of receptor activator of NF-B ligand-expressing T cells are present in chronic human periodontitis tissue (54). However, given that T cells are heterogeneous, their net effect likely reflects the predominant induction of either a pro-(Th1 and Th17) vs anti-inflammatory (Th2 and T regulatory) phenotype.…”

Section: Discussionmentioning

confidence: 99%

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Sasaki¹,

Suzuki

Kent

et al. 2008

The Journal of Immunology

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Periodontal disease is a chronic inflammatory disease in the oral cavity, which culminates in alveolar bone loss. Porphyromonas gingivalis is a consensus periodontal pathogen that has been implicated in adult forms of periodontitis. We previously demonstrated that IL-10-deficient mice exhibit a hyperinflammatory phenotype and are highly susceptible to P. gingivalis-induced periodontitis, indicating an important anti-inflammatory effect of IL-10 in suppressing bone loss. In this study, we analyzed the pathway(s) by which IL-10 deficiency leads to severe P. gingivalis-induced periodontitis. Because Stat3 is essential in IL-10 signaling, immune cell-specific Stat3-deficient mice were subjected to P. gingivalis infection to identify the key IL-10-responsive cells in preventing periodontitis. Myeloid cell-specific Stat3-deficient mice exhibited increased periodontal bone loss (p < 0.001), whereas T cell- and B cell-specific Stat3 mice were resistant, suggesting that macrophages (MP) and/or polymorphonuclear leukocytes are the key target cells normally suppressed by IL-10. Myeloid cell-specific Stat3-deficient mice exhibited elevated gingival CD40L gene expression in vivo compared with wild-type controls (p < 0.01), and Stat3-deficient MPs exhibited vigorous P. gingivalis-stimulated IL-12 production in vitro and induced elevated Ag-specific T cell proliferation compared with wild-type MPs (p < 0.01). Of importance, both IL-12p40/IL-10 and T cell/IL-10 double-deficient mice were resistant to P. gingivalis-induced periodontitis, demonstrating roles for both IL-12p40 and T cells in pathogenesis in a hyperinflammatory model of disease. These data demonstrate that P. gingivalis-induced periodontitis in IL-10-deficient mice is dependent upon IL-12p40-mediated proinflammatory T cell responses.

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“…This may reflect the nature of the respective diseases, in which these cells are involved. To this extent, RANKL in periapical lesions has been particularly associated with fibroblastic cells, rather than T-cells [25], as opposed to periodontitis, where cells of the immune system are considered a major source of RANKL [9,26,27]. When the relative RANKL/OPG ratio was calculated, this was significantly increased in DP cells, compared to PDL cells, indicating a higher capacity for inducing bone resorption by the former cells.…”

Section: P O R P H Y R O Mo N a S G I N G I V A L I S Have Been Stumentioning

confidence: 99%

Oral biofilm challenge regulates the RANKL-OPG system in periodontal ligament and dental pulp cells

Belibasakis

Meier

Guggenheim

et al. 2011

Microbial Pathogenesis

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B and T Lymphocytes Are the Primary Sources of RANKL in the Bone Resorptive Lesion of Periodontal Disease

Abstract: Receptor activator of nuclear factor-B (RANKL)-

Cited by 466 publications

References 57 publications

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Oral biofilm challenge regulates the RANKL-OPG system in periodontal ligament and dental pulp cells

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