Decreased CTLA4(+) and Foxp3(+) CD25(high)CD4(+) cells in induced sputum from patients with mild atopic asthma.

ABSTRACTBackgroundDetails of the comparisons between airway and peripheral blood regulatory T cells (Tregs) in patients with atopic asthma are still unclear. The objective of this study is to investigate the profiles of both airway and circulating Tregs in atopic asthma.MethodsWe measured the numbers of Tregs and eosinophils in induced sputum and peripheral blood in 28 patients with mild atopic asthma and compared these with numbers in 18 healthy controls. The frequency (%) of Tregs (surface CTLA4+, intracellular Foxp3+, and CTLA4+Foxp3+ on CD25highCD4+ T cells) in sputum and blood was determined by intracellular 5-color flow cytometry. We also correlated the numbers with the level of airway hyperresponsiveness (AHR) in asthmatics.ResultsThe mean frequencies of cells expressing CTLA4+ (19.4 ± 2.1%, p = 0.075), Foxp3+ (16.4 ± 3.3%, p = 0.001), and CTLA4+Foxp3+ (7.0 ± 1.1%, p = 0.008) in induced sputum from asthmatics were significantly lower than controls (27.2 ± 3.7%, 37.4 ± 4.7%, and 18.2 ± 3.6%, respectively), whereas in peripheral blood, there was no inter-group difference in the frequencies of cells expressing CTLA4+ (7.1 ±1.5% vs 5.7 ± 1.7%, p > 0.05), Foxp3+ (35.7 ± 3.2% vs 21.1 ± 3.9%, p > 0.05), and CTLA4+Foxp3+ (6.6 ± 1.5% vs 4.2 ± 1.0%, p > 0.05). Moreover, the frequency of CD25highCD4+ cells expressing CTLA4+, but not Foxp3+, in induced sputum was associated with AHR (r = 0.60, p = 0.009) and airway eosinophilic inflammation (r = −0.60, p = 0.008) in asthmatics.ConclusionsAirway, but not circulating, Tregs are decreased in mild atopic asthmatics, and are negatively correlated to an increase of airway eosinophilic inflammation and AHR

Overexpression of CD163, CD204 and CD206 on alveolar macrophages in the lungs of patients with severe chronic obstructive pulmonary disease.

We have previously reported that the lungs of patients with very severe chronic obstructive pulmonary disease (COPD) contain significantly higher numbers of alveolar macrophages than those of non-smokers or smokers. M1 and M2 macrophages represent pro- and anti-inflammatory populations, respectively. However, the roles of M1 and M2 alveolar macrophages in COPD remain unclear. Immunohistochemical techniques were used to examine CD163, CD204 and CD206, as M2 markers, expressed on alveolar macrophages in the lungs of patients with mild to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (mild) n = 11, II (moderate) n = 9, III (severe) n = 2, and IV (very severe) n = 16). Fifteen smokers and 10 non-smokers were also examined for comparison. There were significantly higher numbers of alveolar macrophages in COPD patients than in smokers and non-smokers. The numbers and percentages of CD163(+), CD204(+) or CD206(+) alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers. In patients with COPD, there was a significant negative correlation between the number of CD163(+), CD204(+) or CD206(+) alveolar macrophages and the predicted forced expiratory volume in one second. Overexpression of CD163, CD204 and CD206 on lung alveolar macrophages may be involved in the pathogenesis of COPD

IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma