Imbalance of Th17/Treg cells in mice with chronic cigarette smoke exposure

Wang, Huaying; Peng, Weidong; Weng, Yuesong; Ying, Huajuan; Li, Hequan; Xia, Dajing; Yu, Wanjun

doi:10.1016/j.intimp.2012.09.011

Cited by 58 publications

(54 citation statements)

References 45 publications

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“…These findings are in line with a previous demonstration of increased expression of IFNγ and of STAT4, its downstream transcription factor, in bronchial biopsies from patients with stable COPD 159. IL-23 induces the proliferation of memory T-cells and the secretion of IFNγ, and in animal models cigarette smoking increases the lung expression of IL-23 156,157. IL-17A production by Th17 cells is induced by IL-23 160,161.…”

Section: Individual Cytokines Involved In the Pathogenesis Of Copdsupporting

confidence: 91%

“…In animal models, chronic cigarette smoke exposure increases the expression of IL-23 in the lungs 156,157. In bronchial mucosa, immunostaining for IL-23 is localized in endothelial cells, inflammatory cells, and fibroblasts, and the number of IL-23 + immunoreactive cells is increased in the bronchial epithelium of stable COPD patients compared with control groups,24 but in the human lung there is no significant difference in the expression of IL-23R between COPD and control groups 158.…”

Section: Individual Cytokines Involved In the Pathogenesis Of Copdmentioning

confidence: 99%

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Cytokine inhibition in the treatment of COPD

Caramori¹,

Adcock²,

Stefano³

et al. 2014

COPD

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Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD. The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit. Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either. Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned. There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target. Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond.

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Section: Individual Cytokines Involved In the Pathogenesis Of Copdsupporting

confidence: 91%

Section: Individual Cytokines Involved In the Pathogenesis Of Copdmentioning

confidence: 99%

Cytokine inhibition in the treatment of COPD

Caramori¹,

Adcock²,

Stefano³

et al. 2014

COPD

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“…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). Here, we also show that prior smoke exposure increased production of IL-6, a cytokine that favors Th17 cells (35).…”

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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“…In mice, CS can increase T H 17 cells but only after relatively longterm exposure [59]. Therefore, with chronic CS exposure and resultant sustained IL-17 stimulation, there is perhaps polarization to a neutrophil subtype that is compromised in the ability to clear MTB infection [48].…”

Section: Effects Of Cs On T H 1 T H 2 and T H 17 Cells And Implicatmentioning

confidence: 99%