Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesion Development and Their Chemoattraction Manipulation as a Therapeutic Tool

Francisconi, Carolina Fávaro; Vieira, Andreia; Biguetti, Cláudia Cristina; Glowacki, Andrew J.; Trombone, Ana Paula; Letra, Ariadne; Silva, Renato; Sfeir, Charles; Little, Steven R.; Garlet, Gustavo

doi:10.1016/j.joen.2015.09.022

Cited by 36 publications

(56 citation statements)

References 35 publications

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“…Promising results show attenuation of alveolar bone resorption and inflammation, attributed to the downregulation in the expression of RORγt, IL‐17 and RANKL in Th17 lymphocytes and the upregulation of Treg response by increasing their number and increasing the expression of IL‐10 and TGF‐β1 . Conversely, other studies have reported that immunization with P. gingivalis favours the polarization of Th17 response and the subsequent alveolar bone loss by inducing the RANKL production . These conflicting results are discussed by the authors, who argue that concentration of inoculated bacteria and periodontitis induction methods that are used may modify the expected events.…”

Section: Discussionmentioning

confidence: 99%

“…12,31 Conversely, other studies have reported that immunization with P. gingivalis favours the polarization of Th17 response and the subsequent alveolar bone loss by inducing the RANKL production. 26,32 These conflicting results are discussed by the authors, 12,33 who argue that concentration of inoculated bacteria and periodontitis induction methods that are used may modify the expected events. For instance, subcutaneous injection with formalin-killed bacteria could have a protective effect in comparison with using live bacteria.…”

Section: Interventions For Immuno-modulation Targeting Tregsmentioning

confidence: 99%

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The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review

Cafferata

Jerez

Vernal

et al. 2018

J of Periodontal Research

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This systematic review aimed to: (a) generate a descriptive synthesis of preclinical studies assessing the therapeutic potential of regulatory T lymphocytes (Tregs) to arrest periodontitis, (b) evaluate the methodological heterogeneity of the reviewed animal studies and (c) assess the risk of bias (RoB) of the included studies. The electronic search for animal studies included the MEDLINE, EMBASE, Web of Science and LILACS databases. In addition, a manual search assessed the high‐ranked scientific journals in “periodontics/immunology” and the references listed in the included studies. There were no language, year or publication status restrictions. Two independent reviewers selected and extracted the data, and Cohen's Kappa coefficient was calculated to determine the inter‐examiner agreement. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) tool was used to assess the RoB. A total of 21 of the 425 studies obtained from the database search were included. Treg function was mainly described in Porphyromonas gingivalis‐induced periodontitis (57.1%) in mice (76.2%), where Treg suppression was strongly related to disease progression and Treg induction was strongly related to immuno‐inflammatory response reduction. Of those 21 studies, eight included eight animal experiments using three distinct therapeutic approaches, including: P. gingivalis‐driven immunization (n = 3), retinoic acid inoculation (n = 2) and anti‐inflammatory molecules in polymeric carriers (n = 3), which could modulate the Treg activity through cytokine production (interleukin‐10 and transforming growth factor‐β1), CC‐chemokine‐ and CC‐chemokine receptor‐mediated chemoattraction (CCL22 and CCR4) or Th17‐associated receptor activator of nuclear factor κB ligand (RANKL) downregulation. However, the studies with animal experiments did not specify the randomization sequences and housing conditions that were used, and therefore, 42.11% of the entries were rated as unclear RoB. Distinct therapeutic strategies involving Tregs could potentially suppress the immuno‐inflammatory response and restore alveolar bone homeostasis during periodontitis. Nevertheless, important methodological variability, poor reporting of treatment effect estimates and unclear RoB suggest using caution when assessing the results of these studies.

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Section: Discussionmentioning

confidence: 99%

Section: Interventions For Immuno-modulation Targeting Tregsmentioning

confidence: 99%

The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review

Cafferata

Jerez

Vernal

et al. 2018

J of Periodontal Research

View full text Add to dashboard Cite

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“…The increased bone destruction in IL-17-deficient animals was correlated with the elevated number of osteoclasts and increased expressions of the bone-resorptive cytokines, IL-1 and MIP-2, in PLs (AlShwaimi et al 2013). In the study by Francisconi et al (2016), experimental PLs in C57Bl/6 mice were induced by pulp exposure and bacterial inoculation. The development of lesions was similar to what was observed in the aforementioned studies, and inhibition of Treg function by anti-GITR or CCR4 depletion resulted in a significant increase in PL severity and lesion evolution rate, associated with the upregulation of proinflammatory, Th1, Th17 and tissue-/bone-destructive markers (IL-1b, IL-17, TNF-a, IFN-c, MMP-2 and RANKL) and downregulation of Tregs and healing markers (Francisconi et al 2016).…”

Section: Animal Studiesmentioning

confidence: 99%

The Presence and involvement of interleukin‐17 in apical periodontitis

2019

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Apical periodontitis (AP) is a chronic inflammatory disease characterized by periapical tissue inflammation and destruction of the associated alveolar bone. It is caused by microbial infections within the root canal and the resultant host immune responses in the periapical tissues. The proinflammatory cytokine interleukin (IL)‐17 has been shown to play an important role in many inflammatory diseases. There is increasing evidence of the presence of IL‐17 in AP, which might be associated with disease pathogenesis. Moreover, several animal studies indicate the potential role of IL‐17 in periapical inflammation and the resultant bone resorption in AP. This article reviews recent studies regarding the collective in vitro, in vivo and clinical evidence of the presence and involvement of IL‐17 in AP. A search related to IL‐17 in apical periodontitis was conducted on PubMed, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts that were included. A total of 25 papers were identified, of the 25 included articles, 7 involved laboratory studies on cell cultures, 11 involved animal experimentations, and 7 were observational studies using human clinical samples. In conclusion, evidence for the presence of IL‐17 in AP from human and animal models is clear. However, there is relatively little information currently available that would highlight the specific role of IL‐17 in AP.

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“…1 Leukocytes are recruited from the periapical tissues in response to intracanal bacterial infection, and the persistence of the antigenic stimulus can result in chronic periapical lesions such as periapical granuloma and radicular cyst. 2 The role of immunological mechanisms in the pathogenesis of periapical lesions has been widely documented. 3 The interplay between immune regulatory mechanisms and effector T cell responses is a crucial Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.…”

Section: Introductionmentioning

confidence: 99%

Treg and Th17 cells in inflammatory periapical disease: a systematic review

et al. 2017

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The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.

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Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesion Development and Their Chemoattraction Manipulation as a Therapeutic Tool

Cited by 36 publications

References 35 publications

The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review

The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review

The Presence and involvement of interleukin‐17 in apical periodontitis

Treg and Th17 cells in inflammatory periapical disease: a systematic review

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