Increased expression of CD4+IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and smokers

Zhang, Jianquan; Chu, Shaoli; Zhong, Xiaoning; Lao, Qifang; Zhou, He; Liang, Yi

doi:10.1016/j.intimp.2012.10.018

Cited by 47 publications

(41 citation statements)

References 27 publications

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“…Exaggerated IL-17 production in the lung hastens bronchoconstriction and asthmatic symptoms (39). Though little is known about the role of Th17 cells in COPD, these cells have been identified in lung biopsies from COPD patients and IL-17 has been detected in the sputum from patients during disease exacerbations (40). Chronic cigarette smoke exposure can tip the balance of Th17 and Tregs by decreasing Foxp3 and IL-10 expression while simultaneously increasing ROR-γT and IL-17 expression (41).…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Lugade

Bogner

Thatcher

et al. 2014

The Journal of Immunology

114

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The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality.

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Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Lugade

Bogner

Thatcher

et al. 2014

The Journal of Immunology

114

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown the rate of elevated CD4 þ IL-17 þ cell (Th17 cells) in chronic lung inflammation [6,7] Administration of IL-17 antibody has been reported to reduce the neutrophil count, and IL-6 and IL-8 levels, and airway inflammation following cigarette smoking [9]. In an alternative mouse model of emphysema the Th17 cells and IL-17A levels were increased in wild-type mice, but attenuated in IL-17A-deficient mice [37].…”

Section: Discussionmentioning

confidence: 99%

Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema

Wei

Zhao

Fan

et al. 2015

Biochemical and Biophysical Research Communications

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“…Previous studies showed that the number of IL-17A positive cells is increased in the submucosa of central and small airways from COPD patients, indicating an important role of this cytokine in the recruitment of inflammatory cells and even in the development of COPD [10,24]. Our observation that mast cells express a considerable amount IL-17A adds important information to this finding, because a role for mast-cell derived IL-17 has only been proposed in the development of joint destruction in rheumatoid arthritis [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence for elevated IL-17 expression in chronic obstructive lung disorders [9,10]. IL-17A is not only expressed by T-cells but also other inflammatory cells including mast cells [11] and it is up-regulated by cigarette smoke exposure in human lung tissue explants [12] being likely involved in inflammatory cell recruitment in smoking-induced lung injury.…”

Section: Introductionmentioning

confidence: 99%

Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers – Is There a Specific Role for Mast Cells?

Nussbaumer-Ochsner¹,

Stolk²,

Silva³

et al. 2015

PLoS ONE

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BackgroundSmoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.MethodsThirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MCT) respectively connective tissue mast cells (MCTC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol.ResultsThe median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances). IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39), for the FEV1% pred. (rs= 0.37) and for FEV1/FVC ratio (rs=0.38) with MCT in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44), there was no correlation for pH or FeNO with cellular distribution in SA.ConclusionsNeutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters.

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Increased expression of CD4+IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and smokers

Cited by 47 publications

References 27 publications

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema

Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers – Is There a Specific Role for Mast Cells?

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