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An analysis of Treg/Th17 cells imbalance associated microRNA networks regulated by moxibustion therapy on Zusanli (ST36) and Shenshu (BL23) in mice with collagen induced arthritis.

ABSTRACT: Moxibustion is an emerging alternative therapy for rheumatoid arthritis (RA) in the eastern world, especially in China. However, the mechanism underlying this condition has not yet been elucidated. This study aimed to explore how moxibustion reduced arthritis by regulating Treg/Th17 cell imbalance and the role of differentiation-associated keynote microRNAs (miRNAs). Moxibustion therapy was administered to mice with collagen-induced arthritis (CIA). The arthritis index, histopathological changes, inflammatory factors, and Treg/Th17 cell balance were analyzed. MiRNAs from CD4+ T cells were analyzed based on the RNA-seq technology. Treg/Th17 cell differentiation-related miRNAs and their target genes were identified from the online database of miRDB, TargetScan, and miRTarBase. The expression of miRNAs and their target genes was verified by quantitative reverse transcription polymerase chain reaction and Western blot analysis. The binding sites of miRNAs and target genes were predicted by miRDB, and the targeting relationship between them was verified by dual-luciferase reporter assay. Arthritis in mice with CIA was reduced by moxibustion therapy, and Treg/Th17 cell imbalance was regulated. Seventeen upregulated and twenty-three downregulated miRNAs were identified in moxibustion-treated mice. Seven upregulated miRNAs, seven downregulated miRNAs, and five Treg/Th17 cell differentiation-associated target genes were predicted. Among them, miR-144-3p and Hif1a were suggested to be the keynote miRNA and target gene, respectively, regulating the Treg/Th17 cell differentiation. In conclusions, moxibustion therapy plays a possible regulatory function in rebalancing Treg/Th17 cells by regulating miR-144-3p and its target gene Hif1a to treat CIA.

SUBMITTER: Zhao C

PROVIDER: S-EPMC6684903 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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An analysis of Treg/Th17 cells imbalance associated microRNA networks regulated by moxibustion therapy on Zusanli (ST36) and Shenshu (BL23) in mice with collagen induced arthritis.

Zhao Chuang C Li Xiaoyan X Yang Yan Y Li Zunyuan Z Li Miao M Tan Qian Q Liang Wei W Liu Zhidan Z

American journal of translational research 20190715 7

Moxibustion is an emerging alternative therapy for rheumatoid arthritis (RA) in the eastern world, especially in China. However, the mechanism underlying this condition has not yet been elucidated. This study aimed to explore how moxibustion reduced arthritis by regulating Treg/Th17 cell imbalance and the role of differentiation-associated keynote microRNAs (miRNAs). Moxibustion therapy was administered to mice with collagen-induced arthritis (CIA). The arthritis index, histopathological changes ...[more]

PMID: 31396316

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Project description:N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and were considered useful for the treatment of rheumatoid arthritis (RA). Recently, several studies suggested that n-3 PUFAs attenuated arthritis in animal model and human, however the mechanism is still unclear. Interleukin 17 (IL-17) is a pro-inflammatory cytokine mainly produced by T helper 17 (Th17) cells which cause tissue inflammation and bone erosion leading to joint destruction. In contrast, regulatory T (Treg) cells down-regulate various immune responses by suppression of naïve T cells. The imbalance between Th17 cells and Tregs cell is important for the pathogenesis of RA. Here, we investigated whether n-3 PUFAs attenuate arthritis in collagen antibody-induced arthritis (CAIA) model. We used fat-1 transgenic mice expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids, leading to abundant n-3 fatty acids without the need of a dietary n-3 supply. Clinical arthritis score was significantly attenuated in fat-1 mice compared to wild type (WT) mice on day 7 (1.6±1.8, p = 0.012) and day 9 (1.5±1.6, p = 0.003). Ankle thickness also decreased significantly in fat-1 mice compared to WT mice (1.82±0.11, p = 0.008). The pathologic finding showed that inflammatory cell infiltration and bone destruction were reduced in fat-1 mice compared to WT. The expression levels of IL-17 and related cytokines including IL-6 and IL-23 decreased in the spleen and ankle joint tissue of fat-1 mice compared to WT mice. Furthermore, Treg cells were expanded in the spleen of fat-1 mice and Treg cell differentiation was significantly higher in fat-1 mice than in wild type (p = 0.038). These data suggest that n-3 PUFAs could attenuate arthritis through increasing the expression of FoxP3 and the differentiation of Treg, while reducing IL-17 production. Therefore, dietary supplementation of n-3 PUFAs could have a therapeutic potential for the treatment of RA.

Project description:ObjectiveThis study sought to explore the role of metabolic disturbance in immunoregulation of gingivitis targeting T helper 17 cells (Th17)/regulatory T cell (Treg).Materials and methodsA total of 20 gingivitis patients and 19 healthy volunteers were recruited. Quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate expression patterns of Forkhead box protein P3 (Foxp3), transforming growth factor-β (TGF-β), retinoid-related orphan receptor-gammat (RORγt) and interleukin 17A (IL-17A) in the peripheral blood lymphocytes of subjects across the two groups. Moreover, the enzyme-linked immunosorbent assay (ELISA) technique was used to detect levels of TGF-β, IL-4, IL-6,TL-10 and L-17A secreted in the plasma as well as the SIgA secreted in saliva. Flow cytometry was used to detect the percentage of CD4+CD25+ Foxp3+Treg cells and the percentage of CD4+IL-17A+ Th17 cells in whole blood of subjects in both groups. Gas chromatography-mass spectrometry (GC-MS) was employed to analyze the plasma metabolites in the gingivitis patient group. Statistical analysis was applied to determine whether the plasma metabolites and related metabolic pathways significantly differed between gingivitis patients and healthy controls. Ingenuity pathway analysis (IPA) was employed to identify the potential relation between the metabolites and the Th17 and Treg related pathway.ResultsThe percentages of CD4+IL17A+Th17 cells and IL-17 significantly increased in the peripheral blood in the gingivitis group. Moreover, the upregulation of IL-17A mRNA and RORγt mRNA were also found in the gingivitis group. However, the percentage of CD4+CD25+ Foxp3+Treg cells and Foxp3 mRNA in the whole blood did not significantly change. However, TGF-β mRNA as well as TGF-β, IL-4, IL-6, IL-10 in the periperial blood and SIgA in the saliva were higher in the gingivitis group. Notably, that the ratio of Th17/Treg cells was significantly increased during peripheral circulation. Furthermore, we identified 18 different metabolites which were differentially expressed in plasma between the gingivitis and healthy control groups. Notably, the levels of cholesterol, glycerol 1-octadecanoate, d-glucose, uric acid, cyclohexaneacetic acid, 3-pyridine, tryptophan, and undecane 2,4-dimethyl were significantly up-regulated. whereas the levels of lactic acid, glycine, linoleic acid, monopalmitic acid, glycerol, palmitic acid, pyruvate, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, 1 5-anhydro d-altrol, and boric acid were down-regulated in the gingivitis group, relative to healthy controls. IPA showed that these metabolites are connected to IL17 signaling, TGF-B signaling, and IL10 signaling, which are related closely to Th17 and Treg pathway.ConclusionOverall, these results showed that disturbance to glycolysis as well as amino and fatty acid metabolism are associated with Th17/Treg balance in gingivitis. Impaired immunometabolism may influence some periodontally involved systemic diseases, hence it is a promising strategy in targeted development of treatment therapies.

Dataset Information

An analysis of Treg/Th17 cells imbalance associated microRNA networks regulated by moxibustion therapy on Zusanli (ST36) and Shenshu (BL23) in mice with collagen induced arthritis.

Publications

An analysis of Treg/Th17 cells imbalance associated microRNA networks regulated by moxibustion therapy on Zusanli (ST36) and Shenshu (BL23) in mice with collagen induced arthritis.

Similar Datasets

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