Regulatory T-cells Infiltrate Periodontal Disease Tissues

Nakajima, Takako Eguchi; Ueki-Maruyama, K.; Oda, Tomoko; Ohsawa, Yutaka; Ito, H.; Seymour, G. J.; Yamazaki, Kazuhisa

doi:10.1177/154405910508400711

Cited by 153 publications

(168 citation statements)

References 21 publications

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“…The elevated number of Treg in periodontitis is in accordance with previous reports suggesting that Treg infiltration could reflect an attempt to control tissue destruction promoted by the chronic inflammatory condition in the gingival tissue via the Th17 response (43)(44)(45)(46). In general, the 15d-PGJ 2 -NC-treated animals showed decreased inflammatory responses, as observed by a significant reduction in the expression of almost all mediators evaluated in the current study (IL-17, IL-6, IL-15, FOXP3, CCL22, IL-10, and TGF-b).…”

Section: Discussionsupporting

confidence: 91%

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Napimoga

Silva

Carregaro

et al. 2012

The Journal of Immunology

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The 15-deoxy-Δ12,14-PG J2 (15d-PGJ2) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nanotechnological formulation as a carrier for 15d-PGJ2, and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D,L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ2. BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 μg/kg 15d-PGJ2-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ2-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 μg/kg 15d-PGJ2-NC had a reduction of CD4+CD25+FOXP3+ cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 μg/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 μg/kg 15d-PGJ2-NC, and high amounts of 15d-PGJ2 were observed in the gingiva. In conclusion, the 15d-PGJ2-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model.

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Section: Discussionsupporting

confidence: 91%

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Napimoga

Silva

Carregaro

et al. 2012

The Journal of Immunology

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“…19 The regulatory T cells infiltrate gingival tissue in periodontal disease, but lesions with bone resorption show reduced numbers of these cells, increased levels of IL-1␤, and osteoclastogenic RANKL, suggesting that TGF-␤1 signaling is affected in the active disease process. 49,50 Consistent with these findings, loss of TGF-␤1-mediated suppression of T cells results in increased production of osteoclastogenic interferon-␥, TNF-␣, and RANKL, and in bone loss. 51,52 Although a role for keratinocytes in the immunoregulation of periodontal disease has been proposed, the specific functions of cell surface receptors and their ligands, such as ␣v␤6 integrin and TGF-␤1, have not yet been investigated.…”

Section: Discussionsupporting

confidence: 59%

Absence of αvβ6 Integrin Is Linked to Initiation and Progression of Periodontal Disease

Ghannad

Nica

Fulle

et al. 2008

The American Journal of Pathology

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Integrin ␣v␤6 is generally not expressed in adult epithelia but is induced in wound healing, cancer, and certain fibrotic disorders. Despite this generalized absence, we observed that ␣v␤6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of ␣v␤6 integrin was down-regulated in human periodontal disease, a common medical condition causing tooth loss and also contributing to the development of cardiovascular diseases by increasing the total systemic inflammatory burden. Remarkably, integrin ␤6 knockout mice developed classic signs of spontaneous, chronic periodontal disease with characteristic inflammation, epithelial down-growth, pocket formation, and bone loss around the teeth. Integrin ␣v␤6 acts as a major activator of transforming growth factor-␤1 (TGF-␤1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-␤1 and ␣v␤6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks ␣v␤6 integrin-mediated activation of TGF-␤1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, ␣v␤6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-␤1. (Am J Pathol

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“…21 Ernst et al found that the frequency of forkhead box P3 (FoxP3)/CD25 double-positive cells was strikingly reduced in bone resorption lesions occurring in cases of periodontal disease, with a corresponding increase in RANKL 1 T cells. 22 Kelchtermans et al found that activated CD4 1 CD25 1 Treg cells improve the clinical symptoms of collagen induced arthritis, regulate cytokine production and inhibit osteoclastogenesis both in vitro and in vivo.…”

Section: Modulation Of Treg Cells On Osteoclast Functionsmentioning

confidence: 99%

Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

et al. 2010

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Cross-talk has been shown to occur between the immune system and bone metabolism pathways. In the present study, we investigated the impact of CD4 1 CD25 1 Foxp3 1 regulatory T (Treg) cells on osteoclastogenesis and bone resorption. Treg cells that were isolated and purified from peripheral blood mononuclear cells (PBMCs) of healthy adults inhibited both the differentiation of osteoclasts (OCs) from human embryo bone marrow cells (BMCs) and the pit formation in a dose-dependent manner. In cell cocultures, the production levels of both interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-b1) were proportionally upregulated as the ratio of Treg cells to BMCs was increased, and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-b1 antibodies. Treatment of BMC and Treg cell cocultures with 17b-estradiol (E2) at concentrations between 10 27 and 10 29 mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone; this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression. These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-b1. E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-b1 secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis (PMO).

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Regulatory T-cells Infiltrate Periodontal Disease Tissues

Cited by 153 publications

References 21 publications

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Absence of αvβ6 Integrin Is Linked to Initiation and Progression of Periodontal Disease

Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

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