Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.

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Schistosoma mansoni-Mediated Suppression of Allergic Airway Inflammation Requires Patency and Foxp3+ Treg Cells

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0002379 ◽

2013 ◽

Vol 7 (8) ◽

pp. e2379 ◽

Cited By ~ 33

Author(s):

Laura E. Layland ◽

Kathrin Straubinger ◽

Manuel Ritter ◽

Eva Loffredo-Verde ◽

Holger Garn ◽

...

Keyword(s):

Schistosoma Mansoni ◽

Airway Inflammation ◽

Allergic Airway Inflammation ◽

Treg Cells

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Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500932 ◽

2016 ◽

Vol 44 (08) ◽

pp. 1663-1674 ◽

Cited By ~ 3

Author(s):

Da-In Lee ◽

Mi-Kyung Park ◽

Shin Ae Kang ◽

Jun-Ho Choi ◽

Seok-Jung Kang ◽

...

Keyword(s):

Airway Inflammation ◽

Sea Cucumber ◽

Cell Activation ◽

Biological Effects ◽

Oral Treatment ◽

Allergic Airway Inflammation ◽

Treg Cells ◽

Mesenteric Lymph Nodes ◽

Anti Cancer ◽

Anti Oxidant

Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

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Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

Journal of Immunology Research ◽

10.1155/2021/8816055 ◽

2021 ◽

Vol 2021 ◽

pp. 1-20

Author(s):

Muhua Huang ◽

Jingcheng Dong

Keyword(s):

T Cells ◽

Immune Responses ◽

Airway Inflammation ◽

Tumor Immunity ◽

Allergic Airway Inflammation ◽

Treg Cells ◽

T Helper ◽

Th Cells ◽

Th9 Cells ◽

And Function

CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

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Artepillin C Reduces Allergic Airway Inflammation by Induction of Monocytic Myeloid-Derived Suppressor Cells

Pharmaceutics ◽

10.3390/pharmaceutics13111763 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1763

Author(s):

Núbia Sabrina Martins ◽

Thais Fernanda de Campos Fraga-Silva ◽

Giseli Furlan Correa ◽

Mèdéton Mahoussi Michaël Boko ◽

Leandra Naira Zambelli Ramalho ◽

...

Keyword(s):

Airway Inflammation ◽

Allergic Asthma ◽

Allergic Airway Inflammation ◽

Suppressor Cells ◽

Treg Cells ◽

Transfer Model ◽

Myeloid Derived Suppressor Cells ◽

Asthma Model ◽

Artepillin C ◽

Anti Inflammatory

Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.

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CD103 integrin identifies a high IL-10-producing FoxP3 + regulatory T cell population suppressing allergic airway inflammation

10.22541/au.163251243.34220148/v1 ◽

2021 ◽

Author(s):

Sofia Tagkareli ◽

Maria Salagianni ◽

Ioanna Galani ◽

Maria Manioudaki ◽

Eleftherios Pavlos ◽

...

Keyword(s):

T Cell ◽

Mouse Model ◽

Airway Inflammation ◽

Cell Population ◽

Regulatory T Cell ◽

Inflammatory Responses ◽

Allergic Inflammation ◽

Allergic Airway Inflammation ◽

Treg Cells ◽

Dependent Manner

Background: Although FoxP3 regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the disease context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. Objective: This study aimed at characterizing distinct FoxP3 Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3 Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model ( Foxp3Cd103) enabling the specific ablation of CD103 FoxP3 Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3 Treg cells expressed the integrin CD103 which marks FoxP3 Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103 FoxP3 Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3Cd103 mice lead to severe alveocapillary damage, eosinophilic pneumonia, and markedly reduced lifespan of the animals. Conversely, adoptive transfer of CD103 FoxP3 Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.

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CD103 integrin identifies a high IL-10-producing FoxP3+ regulatory T cell population suppressing allergic airway inflammation

10.22541/au.161636344.42740408/v1 ◽

2021 ◽

Author(s):

Sofia Tagkareli ◽

Maria Salagianni ◽

Ioanna Galani ◽

Maria Manioudaki ◽

Eleftherios Pavlos ◽

...

Keyword(s):

T Cell ◽

Mouse Model ◽

Airway Inflammation ◽

Cell Population ◽

Regulatory T Cell ◽

Inflammatory Responses ◽

Allergic Inflammation ◽

Allergic Airway Inflammation ◽

Treg Cells ◽

Dependent Manner

Background: Although FoxP3+ regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. This study aimed at characterizing distinct FoxP3+ Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3+ Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model (Foxp3creCd103dtr) enabling the specific ablation of CD103+FoxP3+ Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3+ Treg cells expressed the integrin CD103 which marks FoxP3+ Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103+FoxP3+ Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3creCd103dtr mice lead to severe alveocapillary damage and eosinophilic pneumonia, markedly reducing the lifespan of the experimental animals. Conversely, adoptive transfer of CD103+FoxP3+ Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.

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