The Experts below are selected from a list of 14817 Experts worldwide ranked by ideXlab platform
Yong Zhao - One of the best experts on this subject based on the ideXlab platform.
-
The amino acid sensor general control nonderepressible 2 (GCN2) controls TH9 cells and Allergic Airway Inflammation.
The Journal of allergy and clinical immunology, 2019Co-Authors: Peng Wang, Jiayu Zhang, Lu Shi, Tong Lei, Yangxiao Hou, Yong ZhaoAbstract:Background TH9 cells have emerged as important mediators of Allergic Airway Inflammation. There is evidence that general control nonderepressible 2 (GCN2) affects the immune response under some stress conditions. However, whether GCN2 regulates CD4+ T-cell differentiation during Allergic Inflammation remains unknown. Objective We sought to clarify the regulatory roles of GCN2 in CD4+ T-cell subset differentiation and its significance in patients with Allergic Airway Inflammation. Methods The effects of GCN2 in differentiation of TH cell subsets were detected by using the in vitro induction system. GCN2 knockout mice, ovalbumin-induced Allergic Airway Inflammation, and adoptive transfer mouse models were used to determine the significance of GCN2 in TH9 differentiation and Allergic Airway Inflammation in vivo. RNA sequencing, real-time PCR, Western blotting, and other molecular approaches were used to identify the molecular mechanisms relevant to regulation of GCN2 in TH9 cell differentiation. Results GCN2 deficiency significantly inhibited differentiation of TH9 cells but not TH1, TH2, and regulatory T cells. GCN2 knockout mice and recombination-activating gene 2 knockout (Rag2KO) mice that received adoptively transferred GCN2-deficient CD4+ T cells exhibited reduced TH9 differentiation and less severe Allergic Airway Inflammation. Furthermore, the isolated GCN2-deficient TH9 cells also mediated less severe Allergic Airway Inflammation on adoptive transfer. Mechanistically, GCN2 deficiency inhibits TH9 cell differentiation through a hypoxia-inducible factor 1α–dependent glycolytic pathway. Conclusion Our results reveal a novel role of GCN2 in TH9 cell differentiation. Our findings indicate that new strategies to inhibit GCN2 activity might provide novel approaches to attenuate Allergic Airway Inflammation.
-
Phosphatase wild-type p53-induced phosphatase 1 controls the development of TH9 cells and Allergic Airway Inflammation
The Journal of allergy and clinical immunology, 2017Co-Authors: Peng Wang, Lianjun Zhang, Hui Chen, Fan Yang, Lianfeng Zhang, Yong ZhaoAbstract:Background Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far. Objective We sought to identify new molecular targets for T H 9 cell–mediated Allergic Airway Inflammation. Methods Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor–treated mice, and ovalbumin-induced Allergic Airway Inflammation mouse models were used to characterize the roles of Wip1 in Allergic Airway Inflammation. The induction of T H cell subsets in vitro , real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in T H 9 differentiation. Results Here we demonstrate that Wip1-deficient mice are less prone to Allergic Airway Inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates Allergic Inflammation progression. Intriguingly, Wip1 selectively impaired T H 9 but not T H 1, T H 2, and T H 17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase–dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription. Conclusion Wip1 controls T H 9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of Allergic Airway Inflammation. These findings shed light on the previously unrecognized roles of Wip1 in T H 9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of Allergic Airway Inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies.
-
phosphatase wild type p53 induced phosphatase 1 controls the development of t h 9 cells and Allergic Airway Inflammation
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Peng Wang, Lianjun Zhang, Hui Chen, Fan Yang, Lianfeng Zhang, Yong ZhaoAbstract:Background Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far. Objective We sought to identify new molecular targets for T H 9 cell–mediated Allergic Airway Inflammation. Methods Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor–treated mice, and ovalbumin-induced Allergic Airway Inflammation mouse models were used to characterize the roles of Wip1 in Allergic Airway Inflammation. The induction of T H cell subsets in vitro , real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in T H 9 differentiation. Results Here we demonstrate that Wip1-deficient mice are less prone to Allergic Airway Inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates Allergic Inflammation progression. Intriguingly, Wip1 selectively impaired T H 9 but not T H 1, T H 2, and T H 17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase–dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription. Conclusion Wip1 controls T H 9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of Allergic Airway Inflammation. These findings shed light on the previously unrecognized roles of Wip1 in T H 9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of Allergic Airway Inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies.
-
mTORC2 controls Th9 polarization and Allergic Airway Inflammation.
Allergy, 2017Co-Authors: Haohong Chen, Liuqi Zhang, Peng Wang, Wei Wang, Zhulang Chu, Xiaodong Zhang, Yong ZhaoAbstract:Background T helper type 9 (Th9) cells, a subpopulation of CD4+ T cells, play a critical role in the pathogenesis of Allergic Airway Inflammation. However, it remains unknown whether mTORC2 regulates Th9 differentiation or function during Allergic Inflammation. Methods T-cell-specific Rictor-deficient mice, a mouse model of Allergic Airway Inflammation induced by ovalbumin (OVA) sensitization and a mouse model of adoptive transfer of induced Th9 cells, were used to address the roles of mTORC2 in the pathogenesis of Allergic Airway Inflammation. The in vitro Th9 induction, multiple colors flow cytometry, real-time PCR, and Western blots were used to investigate the molecular effects of mTORC2 in Th9 induction. Results The differentiation of naive CD4+ T cells into Th9 cells was significantly diminished in the absence of Rictor, the core component of mTORC2. Using a mouse model of Allergic Airway Inflammation induced by OVA sensitization, T-cell-specific Rictor-deficient mice show much less severe Allergic Airway Inflammation characterized by decreased pathological alterations and fibrosis of the lungs, which was accompanied with reduced Th9 differentiation and infiltration. Importantly, the isolated Rictor-deficient Th9 cells mediate less severe Allergic pathogenesis upon adoptive transfer. Rictor deficiency impairs Th9 cell differentiation by reducing IRF4 expression rather than affecting Foxo1/Foxo3a transcriptional activity, which is likely due to decreased Akt and/or STAT6 activation. Conclusions These findings uncover a novel role of mTORC2 in Th9 cell differentiation and may have important implications for therapeutic intervention of Allergic diseases.
Peng Wang - One of the best experts on this subject based on the ideXlab platform.
-
The amino acid sensor general control nonderepressible 2 (GCN2) controls TH9 cells and Allergic Airway Inflammation.
The Journal of allergy and clinical immunology, 2019Co-Authors: Peng Wang, Jiayu Zhang, Lu Shi, Tong Lei, Yangxiao Hou, Yong ZhaoAbstract:Background TH9 cells have emerged as important mediators of Allergic Airway Inflammation. There is evidence that general control nonderepressible 2 (GCN2) affects the immune response under some stress conditions. However, whether GCN2 regulates CD4+ T-cell differentiation during Allergic Inflammation remains unknown. Objective We sought to clarify the regulatory roles of GCN2 in CD4+ T-cell subset differentiation and its significance in patients with Allergic Airway Inflammation. Methods The effects of GCN2 in differentiation of TH cell subsets were detected by using the in vitro induction system. GCN2 knockout mice, ovalbumin-induced Allergic Airway Inflammation, and adoptive transfer mouse models were used to determine the significance of GCN2 in TH9 differentiation and Allergic Airway Inflammation in vivo. RNA sequencing, real-time PCR, Western blotting, and other molecular approaches were used to identify the molecular mechanisms relevant to regulation of GCN2 in TH9 cell differentiation. Results GCN2 deficiency significantly inhibited differentiation of TH9 cells but not TH1, TH2, and regulatory T cells. GCN2 knockout mice and recombination-activating gene 2 knockout (Rag2KO) mice that received adoptively transferred GCN2-deficient CD4+ T cells exhibited reduced TH9 differentiation and less severe Allergic Airway Inflammation. Furthermore, the isolated GCN2-deficient TH9 cells also mediated less severe Allergic Airway Inflammation on adoptive transfer. Mechanistically, GCN2 deficiency inhibits TH9 cell differentiation through a hypoxia-inducible factor 1α–dependent glycolytic pathway. Conclusion Our results reveal a novel role of GCN2 in TH9 cell differentiation. Our findings indicate that new strategies to inhibit GCN2 activity might provide novel approaches to attenuate Allergic Airway Inflammation.
-
Phosphatase wild-type p53-induced phosphatase 1 controls the development of TH9 cells and Allergic Airway Inflammation
The Journal of allergy and clinical immunology, 2017Co-Authors: Peng Wang, Lianjun Zhang, Hui Chen, Fan Yang, Lianfeng Zhang, Yong ZhaoAbstract:Background Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far. Objective We sought to identify new molecular targets for T H 9 cell–mediated Allergic Airway Inflammation. Methods Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor–treated mice, and ovalbumin-induced Allergic Airway Inflammation mouse models were used to characterize the roles of Wip1 in Allergic Airway Inflammation. The induction of T H cell subsets in vitro , real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in T H 9 differentiation. Results Here we demonstrate that Wip1-deficient mice are less prone to Allergic Airway Inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates Allergic Inflammation progression. Intriguingly, Wip1 selectively impaired T H 9 but not T H 1, T H 2, and T H 17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase–dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription. Conclusion Wip1 controls T H 9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of Allergic Airway Inflammation. These findings shed light on the previously unrecognized roles of Wip1 in T H 9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of Allergic Airway Inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies.
-
phosphatase wild type p53 induced phosphatase 1 controls the development of t h 9 cells and Allergic Airway Inflammation
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Peng Wang, Lianjun Zhang, Hui Chen, Fan Yang, Lianfeng Zhang, Yong ZhaoAbstract:Background Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far. Objective We sought to identify new molecular targets for T H 9 cell–mediated Allergic Airway Inflammation. Methods Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor–treated mice, and ovalbumin-induced Allergic Airway Inflammation mouse models were used to characterize the roles of Wip1 in Allergic Airway Inflammation. The induction of T H cell subsets in vitro , real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in T H 9 differentiation. Results Here we demonstrate that Wip1-deficient mice are less prone to Allergic Airway Inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates Allergic Inflammation progression. Intriguingly, Wip1 selectively impaired T H 9 but not T H 1, T H 2, and T H 17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase–dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription. Conclusion Wip1 controls T H 9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of Allergic Airway Inflammation. These findings shed light on the previously unrecognized roles of Wip1 in T H 9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of Allergic Airway Inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies.
-
mTORC2 controls Th9 polarization and Allergic Airway Inflammation.
Allergy, 2017Co-Authors: Haohong Chen, Liuqi Zhang, Peng Wang, Wei Wang, Zhulang Chu, Xiaodong Zhang, Yong ZhaoAbstract:Background T helper type 9 (Th9) cells, a subpopulation of CD4+ T cells, play a critical role in the pathogenesis of Allergic Airway Inflammation. However, it remains unknown whether mTORC2 regulates Th9 differentiation or function during Allergic Inflammation. Methods T-cell-specific Rictor-deficient mice, a mouse model of Allergic Airway Inflammation induced by ovalbumin (OVA) sensitization and a mouse model of adoptive transfer of induced Th9 cells, were used to address the roles of mTORC2 in the pathogenesis of Allergic Airway Inflammation. The in vitro Th9 induction, multiple colors flow cytometry, real-time PCR, and Western blots were used to investigate the molecular effects of mTORC2 in Th9 induction. Results The differentiation of naive CD4+ T cells into Th9 cells was significantly diminished in the absence of Rictor, the core component of mTORC2. Using a mouse model of Allergic Airway Inflammation induced by OVA sensitization, T-cell-specific Rictor-deficient mice show much less severe Allergic Airway Inflammation characterized by decreased pathological alterations and fibrosis of the lungs, which was accompanied with reduced Th9 differentiation and infiltration. Importantly, the isolated Rictor-deficient Th9 cells mediate less severe Allergic pathogenesis upon adoptive transfer. Rictor deficiency impairs Th9 cell differentiation by reducing IRF4 expression rather than affecting Foxo1/Foxo3a transcriptional activity, which is likely due to decreased Akt and/or STAT6 activation. Conclusions These findings uncover a novel role of mTORC2 in Th9 cell differentiation and may have important implications for therapeutic intervention of Allergic diseases.
Rongyu Liu - One of the best experts on this subject based on the ideXlab platform.
-
TLR2 favors OVA-induced Allergic Airway Inflammation in mice through JNK signaling pathway with activation of autophagy.
Life sciences, 2020Co-Authors: Lei Fang, Muzi Wang, Qiying Shen, Peishan Ding, Xue-bo Yan, Rongyu LiuAbstract:Numerous studies indicate that toll-like receptor 2 (TLR2) led to divergent effects in asthma. The occurrence of autophagy in asthma pathogenesis is still incompletely understood. Here, we aimed to investigate the role of TLR2 and the underlying mechanisms in Allergic Airway Inflammation and autophagy activation. C57BL/6 and TLR2 knockout (TLR2-/-) mice were subjected to an ovalbumin (OVA)-immunized Allergic Airway model, and were treated with SP600125. Differential cell counts in bronchoalveolar lavage fluid were determined by Wright's staining. Histological analysis of Airway Inflammation was determined by haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels of OVA-specific immunoglobulin E (IgE), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Proteins expression in lung tissues was detected by western blot, expression of TLR2 was further observed by immunofluorescence. Autophagy activation was determined by western blot and transmission electron microscopy (TEM). TLR2 expression was increased upon OVA challenge, and TLR2 deficiency was associated with decreased Allergic Airway Inflammation. Meanwhile, TLR2 deficiency weakened autophagy activation. Moreover, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 also suppressed OVA-induced Allergic Airway Inflammation and autophagy activation. Interestingly, treating TLR2-/- mice with SP600125 showed similar OVA-induced Allergic Airway Inflammation and autophagy activation compared to that in vehicle-treated TLR2-/- mice. TLR2 might contribute to the maintenance of Allergic Airway Inflammation through JNK signaling pathway accompanying with autophagy activation. These findings may provide a novel signal target for prevention of Allergic Airway Inflammation. Copyright © 2020 Elsevier Inc. All rights reserved.
-
Anti-inflammatory Property of Galectin-1 in a Murine Model of Allergic Airway Inflammation
Journal of immunology research, 2019Co-Authors: Meng-yuan Dai, Muzi Wang, Fang-fang Chen, Rongyu LiuAbstract:Galectin-1 (Gal-1) has immunomodulatory activities in various Allergic inflammatory disorders, but its potential anti-inflammatory properties on Allergic Airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of Allergic Airway Inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an Allergic Airway Inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the Allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the Allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for Allergic Airway Inflammation in a murine model and may be a potential pharmacological target for Allergic Airway inflammatory diseases.
-
Nebulized Lidocaine Ameliorates Allergic Airway Inflammation via Downregulation of TLR2
Molecular immunology, 2018Co-Authors: Lixia Wang, Muzi Wang, Qiying Shen, Shi-hai Zhang, Lei Fang, Rongyu LiuAbstract:Nebulized lidocaine has been suggested to be beneficial in asthma therapy, but the underlying mechanisms are little known. We aimed to investigate whether Toll-like receptor (TLR) 2 was involved in the protective effect of lidocaine on Allergic Airway Inflammation. Female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Meanwhile, some of the mice were treated with TLR2 agonist (Pam3CSK4, 100 μg) intraperitoneally in combination with OVA on day 0. Just after allergen provocation, mice were treated with inhaled lidocaine or vehicle for 30 min. In this model, we found that lidocaine markedly attenuated OVA-evoked Airway Inflammation, leukocyte recruitment and mucus production. Moreover, lidocaine abrogated the increased concentrations of T cytokines and TNF-α in bronchoalveolar lavage fluid (BALF) of Allergic mice, as well as reducing the expression of phosphorylated nuclear factor (P-NF)-κBp65 and the NOD-like receptor pyridine containing 3 (NLRP3), which are important for the production of pro-inflammatory cytokines. In addition, our study showed that lidocaine dramatically decreased OVA-induced increased expression of TLR2 in the lung tissues. Furthermore, activation of TLR2 aggravated OVA-challenged Airway Inflammation, meanwhile, it also elevated OVA-induced expression of P-NF-κBp65 and NLRP3 in the lungs. However, lidocaine effectively inhibited Airway Inflammation and counteracted the expression of P-NF-κBp65 and NLRP3 in Allergic mice pretreated with Pam3CSK4. Taken together, the present study demonstrated that lidocaine prevented Allergic Airway Inflammation via TLR2 in an OVA-induced murine Allergic Airway Inflammation model. TLR2/NF-κB/NLRP3 pathway may serve as a promising therapeutic strategy for Allergic Airway Inflammation.
-
JNK-TLR9 signal pathway mediates Allergic Airway Inflammation through suppressing melatonin biosynthesis.
Journal of pineal research, 2016Co-Authors: Qiying Shen, Shi-hai Zhang, Lei Fang, Pei-ting Shen, Yajing Liu, Rongyu LiuAbstract:Toll-like receptors (TLRs) play pivotal role in the pathogenesis of Allergic Airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the Allergic Airway Inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish Allergic Airway disease model. We found that the expression of TLR9 was elevated concomitantly with Airway Inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited Airway Inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA-challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of Allergic Airway Inflammation in OVA-challenged WT mice, but not further ameliorated Allergic Airway Inflammation in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK-TLR9 signal pathway mediates Allergic Airway Inflammation through suppressing melatonin biosynthesis.
Xuejun Guo - One of the best experts on this subject based on the ideXlab platform.
-
TNF-TNFR2 Signaling Inhibits Th2 and Th17 Polarization and Alleviates Allergic Airway Inflammation.
International archives of allergy and immunology, 2019Co-Authors: Juan Peng, Guorui Zhang, Yi Cheng, Xi Chen, Xuejun GuoAbstract:Background TNF-TNFR2 signaling has been indicated to be involved in CD4+ T lymphocyte differentiation. However, its role in Allergic Airway Inflammation is not well understood. Objectives The aim of this study was to investigate the role of TNF-TNFR2 signaling in Allergic Airway Inflammation. Methods and results In this study, we used an allergen-induced asthma model to show that TNF-TNFR2 signaling alleviated Allergic Airway Inflammation by reducing the Airway infiltration of eosinophils and neutrophils. Activated TNF-TNFR2 signaling decreased the expression of Th2 and Th17 cytokines in serum and bronchoalveolar lavage fluid. Furthermore, TNF-TNFR2 signaling inhibited Th2 and Th17 polarization but promoted Th1 and CD4+CD25+ T cell differentiation in vivo. Conclusions Our study indicates that TNF-TNFR2 signaling alleviates Allergic Airway Inflammation through inhibition of Th2 and Th17 cell differentiation.
-
Impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates Allergic Airway Inflammation
American journal of physiology. Lung cellular and molecular physiology, 2017Co-Authors: Xi Chen, Juan Peng, Yi Cheng, Yi-jia Guo, Xuejun GuoAbstract:CD4+ T-cell differentiation plays an important role in Allergic Airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+ T-lymphocyte differentiation, but its role in Allergic Airway Inflammation is not clear. Here, we investigated the role of TNFR2 in Allergic Airway Inflammation. The mouse model was generated by immunization with ovalbumin and intranasal administration of TNFR2 antibody. Airway Inflammation and CD4+ T-cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated Airway Inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid. Impaired TNFR2 signaling promoted Th2 and Th17 polarization but inhibited Th1 and CD4+CD25+ T-cell differentiation in vivo. Furthermore, TNFR2 signaling inhibition promoted Th2 and Th17 polarization in vitro, which may occur through the activation of TNF receptor-associated factor 2 and NF-κB signaling. Therefore, our findings indicate that impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates Allergic Airway Inflammation.
Padraic G Fallon - One of the best experts on this subject based on the ideXlab platform.
-
Regulatory B cells prevent and reverse Allergic Airway Inflammation via FoxP3-positive T regulatory cells in a murine model
The Journal of allergy and clinical immunology, 2010Co-Authors: Sylvie Amu, Sean P. Saunders, Mitchell Kronenberg, Niamh E. Mangan, Ann Atzberger, Padraic G FallonAbstract:Parasitic helminth infections of humans have been shown to suppress the immune response to allergens. Experimentally, infection of mice with the helminth Schistosoma mansoni prevents Allergic Airway Inflammation and anaphylaxis via IL-10 and B cells. To identify and characterize the specific helminth-induced regulatory B-cell subpopulation and determine the mechanism by which these regulatory B cells suppress Allergic Airway Inflammation. IL-10-producing B cells from the spleens of helminth-infected mice were phenotyped, isolated, and transferred to ovalbumin-sensitized mice, and their ability to modulate Allergic Airway Inflammation was analyzed. S mansoni infection induced IL-10-producing CD1d(high) regulatory B cells that could prevent ovalbumin-induced Allergic Airway Inflammation following passive transfer to ovalbumin-sensitized recipients. The capacity of regulatory B cells to suppress Allergic Airway Inflammation was dependent on the expression of CD1d, and they functioned via an IL-10-mediated mechanism. Regulatory B cells induced pulmonary infiltration of CD4(+)CD25(+) forkhead box protein 3(+) regulatory T cells, independent of TGF-beta, thereby suppressing Allergic Airway Inflammation. Regulatory B cells that were generated ex vivo also suppressed the development of Allergic Airway Inflammation. Furthermore, the transfer of regulatory B cells reversed established Airway Inflammation in ovalbumin-sensitized mice. We have generated in vivo and ex vivo a regulatory B cell that can prevent or reverse allergen-induced Airway Inflammation via regulatory T cells. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
-
Regulatory B cells prevent and reverse Allergic Airway Inflammation via FoxP3-positive T regulatory cells in a murine model
Journal of Allergy and Clinical Immunology, 2010Co-Authors: Sylvie Amu, Sean P. Saunders, Mitchell Kronenberg, Niamh E. Mangan, Ann Atzberger, Padraic G FallonAbstract:Background Parasitic helminth infections of humans have been shown to suppress the immune response to allergens. Experimentally, infection of mice with the helminth Schistosoma mansoni prevents Allergic Airway Inflammation and anaphylaxis via IL-10 and B cells. Objective To identify and characterize the specific helminth-induced regulatory B-cell subpopulation and determine the mechanism by which these regulatory B cells suppress Allergic Airway Inflammation. Methods IL-10–producing B cells from the spleens of helminth-infected mice were phenotyped, isolated, and transferred to ovalbumin-sensitized mice, and their ability to modulate Allergic Airway Inflammation was analyzed. Results S mansoni infection induced IL-10–producing CD1d high regulatory B cells that could prevent ovalbumin-induced Allergic Airway Inflammation following passive transfer to ovalbumin-sensitized recipients. The capacity of regulatory B cells to suppress Allergic Airway Inflammation was dependent on the expression of CD1d, and they functioned via an IL-10–mediated mechanism. Regulatory B cells induced pulmonary infiltration of CD4 + CD25 + forkhead box protein 3 + regulatory T cells, independent of TGF-β, thereby suppressing Allergic Airway Inflammation. Regulatory B cells that were generated ex vivo also suppressed the development of Allergic Airway Inflammation. Furthermore, the transfer of regulatory B cells reversed established Airway Inflammation in ovalbumin-sensitized mice. Conclusion We have generated in vivo and ex vivo a regulatory B cell that can prevent or reverse allergen-induced Airway Inflammation via regulatory T cells.
