LPS-miR-34a-CCL22 axis contributes to regulatory T cell recruitment in periapical lesions

He, Maoxian; Song, Gaoyuan; Yu, Yang; Jin, Qiuchen; Bian, Zhuan

doi:10.1016/j.bbrc.2015.03.098

Cited by 12 publications

(12 citation statements)

References 29 publications

(45 reference statements)

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“…Indeed, adoptive transfer of CCR4+ Tregs restore original host response phenotype of CCR4KO mice in experimental periodontitis (22). Similarly, in rats’ experimental periapical lesions, the chemokine CCL22, a CCR4 ligand, was chronologically alleged to mediate Treg appearance and regulatory activity (21). Our results confirm this hypothesis, since CCL22 release in the root canal system (by means of a previously developed degradable PLGA microparticles containing recombinant CCL22 (29)) effectively promotes Treg migration and arrests progression of the lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, decreased expression of Treg phenotypic and functional markers, as well its impaired function due increased FOXp3 methylation, are characteristic features of progressive human periapical lesions (20). Migration of Tregs has been associated with the chemotactic cytokine CCL22 as well as decreased severity of experimental periapical lesion in rats (21). Accordingly, CCL22 interaction with the receptor CCR4 appears to control Treg migration into mice periodontal tissues and consecutively suppresses local inflammatory bone loss (22).…”

Section: Introductionmentioning

confidence: 99%

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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

Francisconi

Vieira

Biguetti

et al. 2016

Journal of Endodontics

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Introduction The pathogenesis of periapical lesions is determined by the balance between host pro-inflammatory immune response and counteracting anti-inflammatory and reparative responses, which include regulatory T cells (Tregs) as potential immunoregulatory agents. In this study, we investigated (in a cause-and-effect manner) the involvement of CCL22-CCR4 axis in Tregs migration to the periapical area and the role of Tregs in the determination of outcomes in periapical lesions. Methods Periapical lesions were induced in C57Bl/6 (WT) and CCR4KO mice (pulp exposure and bacterial inoculation), and treated with anti-GITR to inhibit Tregs function or alternatively with CCL22-releasing, PLGA particles to induce site-specific migration of Tregs. Post treatment, lesions were analyzed for Tregs influx and phenotype, overall periapical bone loss and inflammatory/immunological and wound healing markers expression (analyzed by RealTimePCRarray). Results Tregs inhibition by anti-GITR or CCR4 depletion results in a significant increase in periapical lesions severity, associated with upregulation of proinflammatory, Th1, Th17 and tissue destruction markers in parallel with decreased Tregs and healing markers expression. The local release of CCL22 in the root canal system resulted in the promotion of Tregs migration in a CCR4-dependent manner, leading to the arrest of periapical lesions progression, associated with downregulation of pro-inflammatory, Th1, Th17 and tissue destruction markers in parallel with increased Tregs and healing markers expression. Conclusions Since the natural and CCL22 induced Tregs migration switch active lesion into inactivity phenotype, Tregs chemoattractant may be a promisor strategy for the clinical management of periapical lesions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Francisconi

Vieira

Biguetti

et al. 2016

Journal of Endodontics

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“…The relationship between the inhibitory characteristic of FoxP3 and the proinflammatory feature of IL-17 in the periapical lesions was also highlighted. However, some of the existing articles 33,34 addressing this issue were excluded from this systematic review because they used animal experiments in their methodology, which limits the extension of the results to humans.…”

Section: Limitationsmentioning

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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“…Furthermore, it has been demonstrated that clusterin induces the production of CCL20 by regulating the oxidative stress environment in airway epithelial cells from mice studies (26). Previous studies have demonstrated that microRNA-34a, 15-lipoxygenase and histamine are important regulators for CCL22 in airway epithelial cells (27)(28)(29).…”

Section: Expression Properties Of Epithelial Chemokinesmentioning

confidence: 99%

“…CCR3 and CCR4 surface receptors of Th2 cells directly bind to chemokines secreted by epithelial cells. CCR4 interacts with CCL17/CCL22, and CCR3 interacts with CCL13 (27). Animal studies have indicated that targeted blocking of CCR4/CCR3 receptors can significantly reduce the eosinophil ratio in the bronchoalveolar lavage fluid of asthmatic model mice (47).…”

Section: Functional Properties Of Chemokines and Associations Betweenmentioning

confidence: 99%

Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma (Review)

et al. 2018

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As the first barrier to the outside environment, airway epithelial cells serve a central role in the initiation and development of airway inflammation. Chemokines are the most direct and immediate cell factors for the recruitment and migration of inflammatory cells. The present review focused on the role of epithelial chemokines in the pathogenesis of airway inflammation in asthma. In addition to traditional CC family chemokines and CXC family chemokines, airway epithelial cells also express other chemokines, including thymic stromal lymphopoietin and interleukin‑33. By expressing and secreting chemokines, airway epithelial cells serve a key role in orchestrating airway inflammation in asthma.

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LPS-miR-34a-CCL22 axis contributes to regulatory T cell recruitment in periapical lesions

Cited by 12 publications

References 29 publications

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

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

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

Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma (Review)

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