Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases

Bunte, Kübra; Beikler, Thomas

doi:10.3390/ijms20143394

Cited by 336 publications

(329 citation statements)

References 208 publications

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“…In addition, genes co‐expressed with AIM2 correlate with a number of pathways, including neutrophil activation, leucocyte migration, T‐cell activation, regulation of lymphocyte activation, and lymphocyte differentiation, according to GO analysis, and protein processing in endoplasmic reticulum, chemokine signalling pathway, and osteoclast differentiation in KEGG analysis. Considering the close association between immune inflammation and periodontitis (Bunte & Beikler, ), and the correlation between protein processing in the endoplasmic reticulum and periodontitis (P. Xue et al, ), the results of GO enrichment and KEGG analysis further support a potential role of AIM2 in the pathogenesis of periodontitis.…”

Section: Discussionmentioning

confidence: 78%

Integration of genome‐wide association study and expression quantitative trait loci data identifies AIM2 as a risk gene of periodontitis

Zheng

Meng

et al. 2020

J Clinic Periodontology

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Aim:To identify risk variants associated with gene expression in peripheral blood and to identify genes whose expression change may contribute to the susceptibility to periodontitis. Material and Methods:We systematically integrated the genetic associations from a recent large-scale periodontitis GWAS and blood expression quantitative trait loci (eQTL) data using Sherlock, a Bayesian statistical framework. We then validated the potential causal genes in independent gene expression data sets. Gene co-expression analysis was used to explore the functional relationship for the identified causal genes.Results: Sherlock analysis identified 10 genes (rs7403881 for MT1L, rs12459542 for SIGLEC5, rs12459542 for SIGLEC14, rs6680386 for S100A12, rs10489524 for TRIM33, rs11962642 for HIST1H3E, rs2814770 for AIM2, rs7593959 for FASTKD2, rs10416904 for PKN1, and rs10508204 for WDR37) whose expression may influence periodontitis. Among these genes, AIM2 was consistent significantly upregulated in periodontium of periodontitis patients across four data sets. The cis-eQTL (rs2814770, ~16 kb upstream of AIM2) showed significant association with AIM2 (p = 6.63 × 10 -6 ) and suggestive association with periodontitis (p = 7.52 × 10 -4 ). We also validated the significant association between rs2814770 and AIM2 expression in independent expression data set. Pathway analysis revealed that genes co-expressed with AIM2 were significantly enriched in immune-and inflammation-related pathways. Conclusion:Our findings implicate that AIM2 is a susceptibility gene, expression of which in gingiva may influence periodontitis risk. Further functional investigation of AIM2 may provide new insight for periodontitis pathogenesis. K E Y W O R D SAIM2, eQTL, GWAS, periodontitis, Sherlock

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Section: Discussionmentioning

confidence: 78%

Integration of genome‐wide association study and expression quantitative trait loci data identifies AIM2 as a risk gene of periodontitis

Zheng

Meng

et al. 2020

J Clinic Periodontology

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“…Importantly, in addition to the histopathological findings, we observed in the current study that ligature-induced periodontitis showed the increased concentrations of the cytokines IL-17, IL-6, and IL-4 in the heart of mice with gingival inflammation. The presence of these cytokines, especially IL-17 and IL-6, are strongly associated with cardiovascular alterations 8,44,45 . Corroborating these findings, other experimental studies in mice have also shown high levels of inflammatory mediators in the heart, following systemic administration of bacterial components or periodontal bacteria 42,[46][47][48][49][50][51] , although few studies evaluated the heart cytokines in ligature model.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Ribeiro

Santos-Júnior

Luiz

et al. 2020

Sci Rep

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the present study examined the hemodynamics [arterial pressure (Ap), Ap variability (ApV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/ min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical periodontitis. Periodontitis is caused by a chronic inflammatory response to a periodontal biofilm that deranges the supporting tissues around the teeth (alveolar bone, periodontal ligament, and cementum), causing dental loss 1. This inflammatory disease represents a major public health problem, with an estimated prevalence of over 790 million people worldwide 2,3. Of note, more than 700 species of bacteria are estimated in the oral cavity forming the dental biofilm 4,5. Biofilms can release biologically active products, including bacterial lipopolysaccharides, chemotactic mediators, protein toxins, and organic acids. These active products elicit different components of innate and adaptive immunity 6 followed by the production of inflammatory mediators, mainly cytokines produced by immune cells 7. These cytokines, including interleukin (IL)-17, IL-6, IL-4, and other inflammatory mediators, such as C-reactive protein, are released in response to the stimuli induced by the dental biofilm 8. Different rodent models of periodontal disease have been described to investigate the pathophysiology of this inflammatory disease and accompanying complications 9,10. Nevertheless, the placement of a ligature around a molar tooth is one of the most widely used model 11. Indeed, ligatures around the posterior teeth mimic human periodontitis, leading to local inflammatory cell accumulation, apical migration of junctional epithelium, and bone loss 9,12,13. Moreover, the structure of the dental gingival area in the rodent is quite similar to that exhibited by humans 14. Recent studies have proven that the harmful effects of periodontitis are not re...

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“…In RA, multiple proinflammatory molecules are involved, including increased interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-17 [15][16][17]. In addition to their well-established actions on immune cells [18], these RA-relevant stimuli result in the molecular activation of catabolic and inflammatory processes in human chondrocytes.…”

Section: Chondrocytes Acting As Target Cells In Ramentioning

confidence: 99%

Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

Tseng

Chen

Chang

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.

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Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases

Cited by 336 publications

References 208 publications

Integration of genome‐wide association study and expression quantitative trait loci data identifies AIM2 as a risk gene of periodontitis

Integration of genome‐wide association study and expression quantitative trait loci data identifies AIM2 as a risk gene of periodontitis

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

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