The Immunopathogenesis of Chronic Obstructive Pulmonary Disease: Insights from Recent Research

Curtis, Jeffrey L.; Freeman, Christine M.; Hogg, James C.

doi:10.1513/pats.200701-002fm

Cited by 167 publications

(152 citation statements)

References 133 publications

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“…T-lymphocytes are shown to be extensively present in the alveolar walls of COPD patients and the extent of intrapulmonary lymphocytic infiltrations is correlated with disease severity [2,4,10,22]. It has long been established that CD8+ cells play a major role in the pathogenesis of COPD and that these cells are abundantly present in the airways of patients [3,4,10]. It has also been shown that increased COPD disease severity is characterised by an increased cytotoxic potential or cytokine production capacity of CD8+ T-cells in the lung [4,8,10].…”

Section: Effects Of Smoking On Cytokine Expressionmentioning

confidence: 99%

“…It has long been established that CD8+ cells play a major role in the pathogenesis of COPD and that these cells are abundantly present in the airways of patients [3,4,10]. It has also been shown that increased COPD disease severity is characterised by an increased cytotoxic potential or cytokine production capacity of CD8+ T-cells in the lung [4,8,10]. Besides the local inflammation, it is now clear that also systemic inflammation is of great importance in the pathogenesis of COPD [23].…”

Section: Effects Of Smoking On Cytokine Expressionmentioning

confidence: 99%

“…Several reports have shown that increased bronchus obstruction correlates with increased interferon (IFN)-c production by lung CD8+ T-cells [5][6][7] and their increased expression of cytotoxic molecules [8]; however, interleukin (IL)-4 production has also been reported [9]. CD4+ T-cells that accumulate in the airways and lungs of patients also mainly produce IFN-c and therefore have a T-helper 1 (Th1) phenotype [10]. However, recent studies have shown increased expression of Th17 cytokines in bronchial mucosa and sputum of patients, indicating a role for this novel T-helper subtype in COPD [11][12][13].…”

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Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

et al. 2011

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Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. Both CD4+ and CD8+ T-lymphocytes play a key role in COPD pathogenesis, but cytokine profiles in circulating T-lymphocytes have not been well characterised.Here we report the analysis of peripheral blood T-cells from 30 stable COPD patients and 10 healthy never-smokers for interferon (IFN)-c, interleukin (IL)-4, tumour necrosis factor (TNF)-a and the T-helper 17 cytokines IL-17A, IL-17F and IL-22 by intracellular flow cytometry.We found significantly increased proportions of IFN-c+ and TNF-a+ CD8+ T-cells in COPD patients, when compared with healthy controls. This was most evident in patients with less severe disease. In contrast, expression profiles in circulating CD4+ T-cells were similar in COPD patients and healthy controls for all cytokines tested, except for IL-17F. COPD patients with more severely reduced diffusing capacity had lower proportions of IL-17A+ CD4+ T-cells. Proportions of IL-22+ cells in the CD4+ memory T-cell population were significantly increased in active smokers, when compared with past smokers.Collectively, this comprehensive cytokine analysis of circulating T-cells in COPD patients revealed a correlation for CD8+ T-cells between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and IFN-c or TNF-a expression, but not for CD4+ T-cells.

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Section: Effects Of Smoking On Cytokine Expressionmentioning

confidence: 99%

Section: Effects Of Smoking On Cytokine Expressionmentioning

confidence: 99%

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confidence: 99%

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Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

et al. 2011

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“…2006; Curtis et al. 2007). It is widely accepted that chronic inflammation contributes to the pathogenesis of COPD.…”

Section: Introductionmentioning

confidence: 99%

Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

Morissette

Gao

Shen

et al. 2016

Physiological Reports

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Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B‐cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke‐induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF. Blockade of BAFF using a BAFF receptor‐Fc (BAFFR‐Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR‐Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke‐induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B‐cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke‐induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke‐induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking.

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“…The disease is characterized by the development of airflow limitation, which is slowly progressive and poorly reversible. The airflow limitation is due to a combination of chronic obstructive bronchiolitis, destruction of lung parenchyma (emphysema), and structural alterations of the small airways (2). Cigarette smoking is the major risk factor for the development of COPD, and it has been shown that chronic exposure to cigarette smoke (CS) leads to an abnormal inflammatory response of the lungs.…”

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confidence: 99%

Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

Vernooy¹,

Bracke

Drummen³

et al. 2010

The Journal of Immunology

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Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p < 0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p < 0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice.

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The Immunopathogenesis of Chronic Obstructive Pulmonary Disease: Insights from Recent Research

Cited by 167 publications

References 133 publications

Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

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