Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation

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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Allergen specific Treg upregulated by lung-stage schistosome infection alleviates allergic airway inflammation via inhibiting IgE secretion

10.1101/2020.04.14.040998 ◽

2020 ◽

Author(s):

Zhi dan Li ◽

Wei Zhang ◽

fang Luo ◽

jian Li ◽

Wen bin Yang ◽

...

Keyword(s):

Mouse Model ◽

Airway Inflammation ◽

Therapeutic Effect ◽

Lung Tissue ◽

Allergic Airway Inflammation ◽

Therapeutic Effects ◽

Protective Effects ◽

Schistosome Infection ◽

Allergen Sensitization ◽

Asthma Attack

Schistosome infection showed protective effects against allergic airway inflammation (AAI). However,controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. Moreover, most previous studies focused on understanding the preventive effect of schistosome infection on asthma (infection before allergen sensitization), while its therapeutic effects (infection after allergen sensitization) were rarely investigated. In this study, we investigated the therapeutic effects of schistosome infection on AAI using a mouse model of OVA induced asthma. To explore how the timing of schistosome infection influences its therapeutic effect, the mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day before OVA induced asthma attack (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage schistosome infection could relieve OVA induced asthma in a mouse model. The therapeutic effect was mediated by the upregulated OVA specific Treg which suppressed IgE production and Th2 cytokine secretion. Our results may facilitate the discovery of a new therapy for AAI.

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Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma

Clinical & Investigative Medicine ◽

10.25011/cim.v33i3.13726 ◽

2010 ◽

Vol 33 (3) ◽

pp. 196 ◽

Cited By ~ 4

Author(s):

Xia Ke ◽

Jiangju Huang ◽

Quan Chen ◽

Suling Hong ◽

Daoyin Zhu

Keyword(s):

Airway Inflammation ◽

Allergic Asthma ◽

Mycobacterium Bovis ◽

Immunoglobulin E ◽

Allergic Airway Inflammation ◽

Interleukin 12 ◽

Protective Effects ◽

Th2 Response ◽

Bcg Vaccination ◽

Th2 Responses

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.

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Proteomic Analysis of Anti-inflammatory Effects of a Kampo (Japanese Herbal) Medicine “Shoseiryuto (Xiao-Qing-Long-Tang)” on Airway Inflammation in a Mouse Model

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep151 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 26

Author(s):

Takayuki Nagai ◽

Marino Nakao ◽

Yuliko Shimizu ◽

Yoshio Kodera ◽

Masamichi Oh-Ishi ◽

...

Keyword(s):

Herbal Medicine ◽

Mouse Model ◽

Airway Inflammation ◽

Bronchial Asthma ◽

Antibody Titer ◽

Lung Tissue ◽

Proteomic Analysis ◽

Allergic Airway Inflammation ◽

Airway Hyperreactivity ◽

Japanese Herbal Medicine

Effects of a Kampo (Japanese herbal) medicine “shoseiryuto (SST, xiao-qing-long-tang in Chinese)”, which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g kg−1 day−1from day 1 to 6 after OVA inhalation, SST reduced the inflammation in lung tissue, the number of eosinophils and the OVA-specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. SST also reduced the airway hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the agarose two-dimensional electrophoresis showed that the expression of spectrin α2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered the expression. Western blot and immunohistochemical analyses of lung tissue also confirmed this result. When prednisolone was orally administered at 3 mg kg−1 day−1from day 1 to 6 after OVA inhalation, the inflammation in lung tissue, the number of eosinophils in BAL fluids and airway hyperreactivity were reduced in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific IgE antibody titer in BAL fluids and did not recover the expression of spectrin α2 in lung tissue. These results suggest that at least a part of action mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse model is different from that of prednisolone.

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Scrophularia koraiensis Nakai Attenuates Allergic Airway Inflammation via Suppression of NF-κB and Enhancement of Nrf2/HO-1 Signaling

Antioxidants ◽

10.3390/antiox9020099 ◽

2020 ◽

Vol 9 (2) ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Tae-Yang Jung ◽

A Yeong Lee ◽

Jun-Ho Song ◽

Min Young Lee ◽

Je-Oh Lim ◽

...

Keyword(s):

Airway Inflammation ◽

Immunoglobulin E ◽

Allergic Airway Inflammation ◽

Ethanol Extract ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Protective Effects ◽

Mucus Production ◽

Cell Counts

Scrophularia koraiensis Nakai (Scrophulariaceae) is a medicinal herb that grows in Korea and which has been widely used to treat fever, edema, neuritis and laryngitis. Hence, we evaluated the anti-inflammatory and antioxidant effects of the ethanol extract (SKE) of S. koraiensis Nakai in an ovalbumin (OVA)-induced mouse model. We injected 20 μg of OVA with 2 mg of aluminum on day 0 and day 14 to induce allergic airway inflammation in six-week-old BALB/c mice, and mice were challenged with 1% OVA by nebulization for 1 h on days 21, 22, and 23. SKE was orally administered at 20 mg/kg and 40 mg/kg from day 18 to 23, and its effects were compared with those of montelukast treatment. SKE significantly reduced proinflammatory cytokines, inflammatory cell counts, immunoglobulin-E, and airway hyperresponsiveness during the OVA-induced allergic airway inflammation model; it also reduced airway inflammation and mucus production. In addition, SKE reduced the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation in lung tissues while enhancing nuclear factor erythroid-derived 2-related factor (Nrf-2) and heme oxygenase-1 (HO-1) expression. In conclusion, SKE showed the protective effects on OVA-induced allergic airway inflammation via the suppression of NF-κB phosphorylation and the enhancement of the Nrf2/HO-1 signaling pathway. These results indicate that SKE is a potential therapeutic agent for allergic airway inflammation.

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Alcohol reduces airway hyperresponsiveness (AHR) and allergic airway inflammation in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00077.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. L308-L315 ◽

Cited By ~ 17

Author(s):

Peter J. Oldenburg ◽

Jill A. Poole ◽

Joseph H. Sisson

Keyword(s):

Mouse Model ◽

Airway Inflammation ◽

Allergic Asthma ◽

Airway Hyperresponsiveness ◽

Immunoglobulin E ◽

Allergic Airway Inflammation ◽

Alcohol Exposure ◽

Lung Pathology ◽

Cell Counts

There is very limited knowledge about the effects of alcohol on airway hyperresponsiveness and inflammation in asthma. Historical accounts of alcohol administration to patients with breathing problems suggest that alcohol may have bronchodilating properties. We hypothesized that alcohol exposure will alter airway hyperresponsiveness (AHR) and pulmonary inflammation in a mouse model of allergic asthma. To test this hypothesis, BALB/c mice were fed either 18% alcohol or water and then sensitized and challenged with ovalbumin (OVA). AHR was assessed by means of ventilation or barometric plethysmography and reported as either total lung resistance or enhanced pause, respectively. Airway inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluid (BALF), cytokine levels in BALF, lung histology, and serum immunoglobulin E (IgE) levels. Alcohol feeding significantly blocked methacholine-induced increases in AHR compared with water-fed controls. Alcohol feeding significantly reduced total cell numbers (64%) as well as the number of eosinophils (84%) recruited to the lungs of these mice. Modest changes in lung pathology were also observed. Alcohol exposure led to a reduction of IgE in the serum of the EtOH OVA mice. These data demonstrate that alcohol exposure blunts AHR and dampens allergic airway inflammation indices in allergic mice and suggest that there may be an important role for alcohol in the modulation of asthma. These data provide an in vivo basis for previous clinical observations in humans substantiating the bronchodilator properties of alcohol and for the first time demonstrates an alcohol-induced reduction of allergic inflammatory cells in a mouse model of 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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Allergen Specific Treg Upregulated by Lung-stage Schistosome Infection Alleviates Allergic Airway Inflammation via Inhibiting IgE Secretion

10.21203/rs.3.rs-70726/v1 ◽

2020 ◽

Author(s):

Zhi dan Li ◽

Wei Zhang ◽

Fang Luo ◽

Jian Li ◽

Wen bin Yang ◽

...

Keyword(s):

Airway Inflammation ◽

Therapeutic Effect ◽

Lung Tissue ◽

Allergic Airway Inflammation ◽

Specific Ige ◽

Therapeutic Effects ◽

Lung Pathology ◽

Protective Effects ◽

Schistosome Infection

Abstract Background. Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist regarding the timing of helminth infection and the underlying mechanisms. Moreover, the therapeutic effects of schistosome infection on asthma were rarely investigated. Methods. The mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). Lung pathology, inflammatory cytokines, IgE and frequency of Treg were measured to evaluate the therapeutic effect. The modulation of allergen specific Treg were elucidated by adoptive transfer and Treg deletion in vivo. Finally, RNAseq was employed to explore the key molecules and pathways that might contribute to Treg upregulation. Results. We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. Conclusions. Our results proved that lung-stage schistosome infection could relieve OVA induced AAI in mouse model by the upregulated OVA specific Treg, which may facilitate the discovery of a new therapy for 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.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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