Alveolar bone resorption and Th1/Th17‐associated immune response triggered during <i>Aggregatibacter actinomycetemcomitans</i>‐induced experimental periodontitis are serotype‐dependent

Monasterio, Gustavo; Castillo, Francisca; Ibarra, Juan Pablo; Guevara, José Ramón Vielma; Rojas, Leticia; Álvarez, Claudio; Fernández, Baltasar; Agüero, Amaru; Betancur, Daniel; Vernal, Rolando

doi:10.1002/jper.17-0563

Cited by 34 publications

(68 citation statements)

References 75 publications

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“…For example, in the presence of IL‐17, IL‐22 contributes to bleomycin‐mediated inflammation, whereas when IL‐17 is absent, such as in il‐17 ‐/‐ knockout mice, IL‐22 is tissue‐protective . During experimental periodontitis, oral inoculation of A. actinomycetemcomitans induced increased expression of IL‐17 and enhanced detection of CD4 + IL‐17 + RORγt + T lymphocytes within periodontal lesions . In the present study, using the same model of experimental periodontitis, increased levels of IL‐22 as well as enhanced detection of CD4 + IL‐22 + AhR + T lymphocytes were detected.…”

Section: Discussionsupporting

confidence: 51%

“…Eight‐week‐old wild‐type BALB/c mice were periodontally infected by direct micro‐injection of A. actinomycetemcomitans via a 26s‐gauge syringe (Hamilton Company, Reno, NV, USA) placed bilaterally into the palatal interproximal gingiva between the first, second, and third molars as described previously . Injections containing 1 × 10 9 CFU/mL of A. actinomycetemcomitans in 2 μL phosphate‐buffered saline (PBS) were given three times each week throughout the duration of the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Each individual palatal periodontal tissue sample was minced to approximately 1‐mm 3 fragments and manually homogenized in a RNase‐free vial using 1 mL of ice‐cold TRIzol Plus reagent (Invitrogen Corp., Barcelona, Spain), following the manufacturer's instructions. Then, total RNA was isolated and purified as described previously . After quantification in a spectrophotometer (Synergy HT; BioTek Instruments, Inc., Winooski, VT, USA), the first‐strand cDNA was synthesized using 1 μg of total RNA with a reverse transcription kit (SuperScript III; Invitrogen, Grand Island, NY, USA), according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Image data were analyzed using a protocol described previously using an analyzer software (DataViewer software, Bruker, Kontich, Belgium). For SEM analysis, bone loss was quantified at magnification ×30 using a scanning electron microscope (Jeol JSMIT300LV, Jeol Ltd, Tokyo, Japan), determining the area of bone loss as described previously . All data were collected by a single observer who was blind to conditions of the maxilla samples.…”

Section: Methodsmentioning

confidence: 99%

“…The flow cytometry data were analyzed using the WinMDi v.2.9 software (The Scripps Research Institute, La Jolla, CA, USA) and expressed as mean ± SD percentage of positive cells over the total. Alveolar bone loss data were calculated and presented as percentage (micro‐CT) and μm 2 (SEM), and shown as mean ± SD as described previously . Data were statistically analyzed using the SPSS 22.0 software (IBM Corp., Armonk, NY, USA), the normality of data distribution was determined using the Kolmogorov‐Smirnov test, and differences were analyzed using the ANOVA and Bonferroni's post hoc tests.…”

Section: Methodsmentioning

confidence: 99%

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IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Monasterio

Budini

Fernández

et al. 2019

J of Periodontal Research

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Background and Objective Over the past few years, the importance of interleukin‐22 (IL‐22) and T‐helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL‐22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis‐affected patients. In addition, IL‐22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro. However, the destructive potential of IL‐22–expressing AhR+ Th22 lymphocytes over periodontal tissues during periodontitis has not been demonstrated in vivo yet. Therefore, this study aimed to analyze whether IL‐22–expressing CD4+AhR+ T lymphocytes detected in periodontal lesions are associated with alveolar bone resorption during experimental periodontitis. Material and Methods Using a murine model of periodontitis, the expression levels of IL‐22 and AhR, as well as the Th1‐, Th2‐, Th17‐ and T regulatory‐associated cytokines, were analyzed in periodontal lesions using qPCR. The detection of CD4+IL‐22+AhR+ T lymphocytes was analyzed in periodontal lesions and cervical lymph nodes that drain these periodontal lesions using flow cytometry. In addition, the expression of the osteoclastogenic mediator called receptor activator of nuclear factor‐κB ligand (RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally, alveolar bone resorption was analyzed using micro‐computed tomography and scanning electron microscopy, and the bone resorption levels were correlated with IL‐22 and RANKL expression. Results Higher levels of IL‐22, AhR, and RANKL, as well as IL‐1β, IL‐6, IL‐12, IL‐17, IL‐23, and TNF‐α, were expressed in periodontal lesions of infected mice compared with periodontal tissues of sham‐infected and non‐infected controls. Similarly, high RANKL immunoreaction was observed in periodontal tissues of infected mice; however, few or absent RANKL immunoreaction was observed in controls. This association between RANKL and periodontal infection was ratified by western blot. Furthermore, a higher detection of CD4+IL‐22+AhR+ T lymphocytes was found in periodontal lesions and cervical lymph nodes that drain these periodontal lesions in infected mice compared with non‐infected controls. Finally, the increased IL‐22 and RANKL expression showed positive correlation between them and with the augmented alveolar bone resorption observed in experimental periodontal lesions. Conclusion This study demonstrates the increase of IL‐22–expressing CD4+AhR+ T lymphocytes in periodontitis‐affected tissues and shows a positive correlation between IL‐22, RANKL expression, and alveolar bone resorption.

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Section: Discussionsupporting

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Monasterio

Budini

Fernández

et al. 2019

J of Periodontal Research

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The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

Sun

et al. 2019

Clinical & Exp Dental Res

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This study aimed to investigate the relationship between inflammation‐related T‐helper cell polarization and the receptor activator for nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, which is associated with bone resorption or remodeling of chronic periodontitis patients. Gingival crevicular fluid (GCF) and gingival tissues were obtained from periodontally healthy individuals (PH group) and chronic periodontitis patients (CP group). The GCF levels of IFN‐γ, IL‐4, IL‐17, and IL‐10 linked to T‐helper cell polarization toward the Th1, Th2, Th17, and Treg phenotypes, respectively, were determined by ELISA. The expression levels of these cytokines and the polarized T‐helper cells in gingival tissues were assessed through immunohistochemical and immunofluorescence assays. In addition, the RANKL and OPG expression levels in gingival tissues were detected by immunohistochemical assays, and linear regression analysis was used to identify the potential relationship between T‐helper cell polarization and the RANKL/OPG ratio. In total, 22 individuals and 35 patients were enrolled in the present study. In both GCF and gingival tissues, increased levels of IL‐17 and the decreased levels of IL‐4 and IL‐10 were observed in the CP group. When polarized T‐helper cells were identified in gingival tissues, more Th1 and Th17 cells were found in the CP group, whereas more Th2 and Treg cells were found in the PH group. Although there was no significant difference in OPG expression between the two groups, the RANKL/OPG ratio in the CP group was higher than that in the PH group. The linear regression analysis showed that the presence of more Th1 and Th17 cells correlated with a higher RANKL/OPG ratio, whereas the presence of more Th2 cells correlated with a lower RANKL/OPG ratio. Th1 and Th17 cells are positively correlated and Th2 cells are negatively correlated with the RANKL/OPG ratio. Our data suggest that T‐helper cell polarization is closely linked to the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients.

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Capsular‐defective Porphyromonas gingivalis mutant strains induce less alveolar bone resorption than W50 wild‐type strain due to a decreased Th1/Th17 immune response and less osteoclast activity

Monasterio

Fernández

Castillo

et al. 2018

Journal of Periodontology

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Background Encapsulation of Porphyromonas gingivalis has been demonstrated as responsible of several host immunological changes, which have been associated with the pathogenesis of periodontitis. Using a murine model of periodontitis and two isogenic non‐capsulated mutants of P. gingivalis, this study aimed to analyze whether P. gingivalis encapsulation induces more severe alveolar bone resorption, and whether this bone loss is associated with a T‐helper (Th)1 and Th17‐pattern of immune response. Methods Experimental periodontal infections were generated by oral inoculation with the encapsulated W50 wild‐type strain or isogenic non‐encapsulated ΔPG0116‐PG0120 (GPA) and ΔPG0109‐PG0118 (GPC) mutants of P. gingivalis. Periodontal infections induced with the encapsulated HG184 or non‐encapsulated ATCC 33277 strains of P. gingivalis were used as controls. Alveolar bone resorption was analyzed using microcomputed tomography and scanning electron microscopy. The expression levels of Th1, Th2, Th17, or T regulatory‐associated cytokines and RANKL, as well as the periodontal bacterial load, were quantified by quantitative polymerase chain reaction. The detection of Th1 and Th17 lymphocytes was analyzed by flow cytometry. Results In the periodontal lesions, both capsular‐defective knockout mutant strains of P. gingivalis induced less alveolar bone resorption than the encapsulated W50 wild‐type strain. This decreased bone loss was associated with a dismissed RANKL expression, decreased Th1‐ and Th17‐type of cytokine expression, reduced Th1 and Th17 lymphocyte detection, and low osteoclast finding. Conclusion These data demonstrate that encapsulation of P. gingivalis plays a key role in the alveolar bone resorption induced during periodontitis, and this bone loss is associated with a Th1‐ and Th17‐pattern of immune response triggered in the periodontal lesions.

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Alveolar bone resorption and Th1/Th17‐associated immune response triggered during Aggregatibacter actinomycetemcomitans‐induced experimental periodontitis are serotype‐dependent

Cited by 34 publications

References 75 publications

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

Capsular‐defective Porphyromonas gingivalis mutant strains induce less alveolar bone resorption than W50 wild‐type strain due to a decreased Th1/Th17 immune response and less osteoclast activity

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Alveolar bone resorption and Th1/Th17‐associated immune response triggered during Aggregatibacter actinomycetemcomitans‐induced experimental periodontitis are serotype‐dependent

Cited by 34 publications

References 75 publications

IL‐22–expressing CD4+AhR+ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4+AhR+ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

Capsular‐defective Porphyromonas gingivalis mutant strains induce less alveolar bone resorption than W50 wild‐type strain due to a decreased Th1/Th17 immune response and less osteoclast activity

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IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis