scholarly journals Adipose-Derived Stem Cells Ameliorate Allergic Airway Inflammation by Inducing Regulatory T Cells in a Mouse Model of Asthma

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kyu-Sup Cho ◽  
Mi-Kyung Park ◽  
Shin-Ae Kang ◽  
Hee-Young Park ◽  
Sung-Lyong Hong ◽  
...  

Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.

2010 ◽  
Vol 84 (17) ◽  
pp. 8790-8798 ◽  
Author(s):  
Debbie C. P. Lee ◽  
James A. E. Harker ◽  
John S. Tregoning ◽  
Sowsan F. Atabani ◽  
Cecilia Johansson ◽  
...  

ABSTRACT Regulatory CD4+ T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4+ Foxp3+ CD25+ natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25+ natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25+ natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Hongyun Zou ◽  
Li-Xia Wang ◽  
Muzi Wang ◽  
Cheng Cheng ◽  
Shuai Li ◽  
...  

Unresolved inflammation underpins the pathogenesis of allergic airway diseases, such as asthma. Ketamine, accepted as a promising therapy for resistant asthma, has been demonstrated to attenuate allergic airway inflammation. However, the anti-inflammatory mechanism by ketamine in this setting is largely unknown. We aimed to investigate whether autophagy was involved in the protective effect of ketamine on allergic airway inflammation. Female C57BL/6 mice were sensitized to ovalbumin (OVA) and treated with ketamine at 25, 50, or 100 mg/kg prior to OVA challenge. In this model, the pulmonary morphological findings and airway inflammation were significantly inhibited at 50 mg/kg but not at 25 or 100 mg/kg. Moreover, 50 mg/kg ketamine abrogated the increased concentrations of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as activated the expression of phosphorylated mammalian target of rapamycin (p-MTOR) and inhibited autophagy in allergic mice. To confirm whether the effect of 50 mg/kg ketamine on asthma was mediated by inhibiting autophagy, rapamycin was administered to mice sensitized to OVA and exposed to 50 mg/kg ketamine. All of the effect of 50 mg/kg ketamine was reversed by rapamycin treatment, including increased p-MTOR and decreased autophagy. Taken together, the present study demonstrates that 50 mg/kg ketamine inhibits allergic airway inflammation by suppressed autophagy, and this effect is mediated by the activation of MTOR in the lungs of allergic mice.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3380
Author(s):  
Hideaki Kadotani ◽  
Kazuhisa Asai ◽  
Atsushi Miyamoto ◽  
Kohei Iwasaki ◽  
Takahiro Kawai ◽  
...  

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.


2016 ◽  
Vol 77 (10) ◽  
pp. 912-915 ◽  
Author(s):  
Iwona Osińska ◽  
Anna Stelmaszczyk-Emmel ◽  
Małgorzata Polubiec-Kownacka ◽  
Dariusz Dziedzic ◽  
Joanna Domagała-Kulawik

2011 ◽  
Vol 111 (4) ◽  
pp. 1088-1095 ◽  
Author(s):  
Stephanie Neuhaus ◽  
Luzia Seifert ◽  
Wolfgang Vautz ◽  
Jürgen Nolte ◽  
Albrecht Bufe ◽  
...  

Background: A multi-capillary column ion mobility spectrometer (MCC/IMS) was developed to provide a method for the noninvasive diagnosis of lung diseases. The possibility of measuring the exhaled breath of mice was evaluated previously. The aim of the present study was to reveal whether mice affected by airway inflammation can be identified via MCC/IMS. Methods: Ten mice were sensitized and challenged with ovalbumin to induce allergic airway inflammation. The breath and volatile compounds of bronchoalveolar lavage fluid (BALF) were measured by MCC/IMS. Furthermore, histamine, nitric oxide, and arachidonic acid were determined as inflammatory markers in vitro. Results: Six volatile molecules were found in the BALF headspace at a significantly higher concentration in mice with airway inflammation compared with healthy animals. The concentration of substances correlated with the numbers of infiltrating eosinophilic granulocytes. However, substances showing a significantly different concentration in the BALF headspace were not found to be different in exhaled breath. Histamine and nitric oxide were identified by MCC/IMS in vitro but not in the BALF headspace or exhaled breath. Conclusion: Airway inflammation in mice is detectable by the analysis of the BALF headspace via MCC/IMS. Molecules detected in the BALF headspace of asthmatic mice at a higher concentration than in healthy animals may originate from oxidative stress induced by airway inflammation. As already described for humans, we found no correlation between the biomarker concentration in the BALF and the breath of mice. We suggest using the model described here to gain deeper insights into this discrepancy.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Anders Tøndell ◽  
Torolf Moen ◽  
Magne Børset ◽  
Øyvind Salvesen ◽  
Anne Dorthea Rø ◽  
...  

In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN-γhave been observed in peripheral blood. The balance between Th1, Th17, and FoxP3+CD4+T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN-γwas investigated. The fractions of FoxP3+CD4+T cells and Th17 cells were both lower in sarcoidosis compared to controls (P=0.017andP=0.011, resp.). The proportion of Th17 cells positive for IFN-γwas greater in sarcoidosis than controls (median 72.4% versus 31%,P=0.0005) and increased with radiologic stage (N=23,rho=0.45, andP=0.03). IFN-γ+Th17 cells were highly correlated with Th1 cells (N=23,rho=0.64, andP=0.001), and the ratio of IFN-γ+Th17/FoxP3+CD4+T cells was prominently increased in sarcoidosis. IFN-γ+Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN-γcould be a consequence of a Th1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.


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