Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin

Xia, Yang; Zhang, Jinghong; Deng, Wang-Sheng; Li, Chaoqian

doi:10.1590/1414-431x20187127

Cited by 9 publications

(7 citation statements)

References 22 publications

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“…We have shown in previous studies that gdT17 cells are involved in the pathogenesis of asthma induction (26), which was confirmed by the presence of an imbalance in the Th1/Th2 ratio of gdT cells in asthma animal models (27). Inhalation of M. phlei has been shown to correct the Th1/Th2 ratio in asthma (12,13) and reverse the Th1/Th2 ratio of gdT cells thereby reducing lung inflammation.…”

Section: Discussionsupporting

confidence: 57%

Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway

Yao

Zhang

Chen

et al. 2020

Braz J Med Biol Res

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The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (gdT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gammasecretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of gdT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and gdT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in gdT17 cells could be used for the prevention and treatment of asthma.

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Section: Discussionsupporting

confidence: 57%

Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway

Yao

Zhang

Chen

et al. 2020

Braz J Med Biol Res

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“…Furthermore, γδT cell counts are increased in the synovium of patients with RA 10 , 11 . In contrast, Xia Yang has demonstrated that γδ regulatory T cells (γδTregs) mediate the anti-inflammatory response in asthma 12 . Relative amounts of γδT17 cells and γδTregs in joints with or without inflammation have not yet been confirmed.…”

Section: Introductionmentioning

confidence: 99%

Tofacitinib restores the balance of γδTreg/γδT17 cells in rheumatoid arthritis by inhibiting the NLRP3 inflammasome

Yang¹,

Zhan²,

Jin³

et al. 2021

Theranostics

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Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, γδTreg/γδT17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp 3 -/- mice were introduced to assess the influence of NLRP3 on γδT17 cell activation in RA. Results: TOF treatment decreased levels of γδT17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the γδTreg/γδT17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1β via downregulation of NLRP3. Furthermore, experiments using Nlrp3 -/- mice verified that the NLRP3 inflammasome mediated the effect of TOF on γδT17 cell activation. Conclusions: Recovery of γδTreg/γδT17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated γδT17 cell activation.

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“…Nevertheless, literature linking asthma and γδT17 cells are scarce. Our previous study con rmed the involvement of γδT17 in mice models of OVA-induced asthma [15] . M. vaccae atomization prevents allergic bronchial asthma in mice models through reduction of AHR and airway in ammation [16] .…”

Section: Introductionmentioning

confidence: 77%

“…Investigations have demonstrated that pro-in ammatory cytokines and the proportion of percentage of IL-17 + γδT cells are dampened upon RTA-408 exposure, leading to attenuated in ammation in the airways of asthma mice models stimulated by ozone [14] . Prior research has established the involvement of γδT17 in asthma [15] . Nevertheless, literature linking asthma and γδT17 cells are scarce.…”

Section: Introductionmentioning

confidence: 99%

Jagged2-γδT17 is Regulated by Mycobacterium Vaccae in Asthmatic Mice

Yao

Sun

Zhang³

et al. 2021

Preprint

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Background: Mycobacterium vaccae nebulization imparted protective effect against asthma in a mouse model. The Jagged2-γδT17 signal transduction pathway plays an important role in bronchial asthma. However, the effect of M. vaccae nebulization on the Jagged2-γδT17 signal transduction pathway in mouse models of asthma remains unclear. Methods: In total, 30 female C57 mice were randomized to normal control (group a), asthma control (group b), M. vaccae nebulization prevention,and M. vaccae nebulization treatment (group d) groups. Asthma mice models were created using ovalbumin (OVA). The Notch signaling pathway was blocked by DAPT inhibitors. Airway hyperreactivity (AHR) was measured by noninvasive lung function tests. Histopathological analyses using blue-periodic acid Schiff along with hematoxylin and eosin were performed. Immunohistochemistry, immunofluorescence, and a Western blotting assay allowed for the detection of lung protein expressions, while spleen expressions of IL-17+γδT+ cytokines were assessed with FLOW cytometry. One-way analysis of variance for within-group comparisons, the least significant difference t-test or Student-Newman-Keuls test for intergroup comparisons, and the nonparametric rank sum test for analysis of airway inflammation scores were used in the study. Results: Asthmatic mice models demonstrated downregulated Notch signaling pathway activation and decreased γδT cells and IL-17 cytokine secretion. There was also increased Jagged2 protein expression which correlated positively with γδT+IL-17+ secretion. In asthmatic mice, the expressions of Jagged2 and γδT17, along with airway inflammation and airway reactivity, were all decreased after M. vaccae exposure (p<0.05). Conclusion: The Notch signaling pathway contributed towards asthma initiation and progression by facilitating γδT cells and IL-17 cytokines production. Inhaled M. vaccae led to a significant decrease in Jagged2 and γδT17 expressions in asthmatic mice, indicating its utility in asthma prevention.

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Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin

Cited by 9 publications

References 22 publications

Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway

Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway

Tofacitinib restores the balance of γδTreg/γδT17 cells in rheumatoid arthritis by inhibiting the NLRP3 inflammasome

Jagged2-γδT17 is Regulated by Mycobacterium Vaccae in Asthmatic Mice

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