Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking

Ström, Jonas Eriksson; Pourazar, Jamshid; Linder, Robert; Blomberg, Anders; Lindberg, Anne; Bucht, Anders; Behndig, Annelie F.

doi:10.1186/s12931-018-0940-7

Cited by 19 publications

(17 citation statements)

References 30 publications

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“…The converse trends between the blood and BAL were also seen with respect to CD4 + cells in a patient study of smokers with COPD. Smoking was found to increase the number of CD8 + T cells and CD8 + NKT-like cells in the BAL of COPD patients with a concurrent reduction of CD4 + cells in the BAL and increase of CD4 + in the blood as previously reported (120, 121), while another study found an increase in iNKT and NKT-like cells in BAL fluid from current smokers but not COPD patients (121). Indeed, the role of iNKT cells in COPD may more relate to exacerbations, which can be caused by infection with respiratory viruses and other pathogens.…”

Section: Role Of Unconventional T Cells In Chronic Lung Disorderssupporting

confidence: 79%

The Influence of Innate Lymphoid Cells and Unconventional T Cells in Chronic Inflammatory Lung Disease

2019

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The lungs are continuously subjected to environmental insults making them susceptible to infection and injury. They are protected by the respiratory epithelium, which not only serves as a physical barrier but also a reactive one that can release cytokines, chemokines, and other defense proteins in response to danger signals, and can undergo conversion to protective mucus-producing goblet cells. The lungs are also guarded by a complex network of highly specialized immune cells and their mediators to support tissue homeostasis and resolve integrity deviation. This review focuses on specialized innate-like lymphocytes present in the lung that act as key sensors of lung insults and direct the pulmonary immune response. Included amongst these tissue-resident lymphocytes are innate lymphoid cells (ILCs), which are classified into five distinct subsets (natural killer, ILC1, ILC2, ILC3, lymphoid tissue-inducer cells), and unconventional T cells including natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ-T cells. While ILCs and unconventional T cells together comprise only a small proportion of the total immune cells in the lung, they have been found to promote lung homeostasis and are emerging as contributors to a variety of chronic lung diseases including pulmonary fibrosis, allergic airway inflammation, and chronic obstructive pulmonary disease (COPD). A particularly intriguing trait of ILCs that has recently emerged is their plasticity and ability to alter their gene expression profiles and adapt their function in response to environmental cues. The malleable nature of these cells may aid in rapid responses to pathogen but may also have downstream pathological consequences. The role of ILC2s in Th2 allergic airway responses is becoming apparent but the contribution of other ILCs and unconventional T cells during chronic lung inflammation is poorly described. This review presents an overview of our current understanding of the involvement of ILCs and unconventional T cells in chronic pulmonary diseases.

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Section: Role Of Unconventional T Cells In Chronic Lung Disorderssupporting

confidence: 79%

The Influence of Innate Lymphoid Cells and Unconventional T Cells in Chronic Inflammatory Lung Disease

2019

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“…Focusing on regulatory immune cells, the aim was to assess the distribution of Tregs in COPD in general and its association with disease status, smoking status and rapid/non-rapid decline in LF in particular. Findings related to cytotoxic immune cells have been reported previously [ 4 ].…”

Section: Introductionsupporting

confidence: 63%

“…Macrophages are thought to play a major role as they can release matrix metalloproteinases capable of degrading the extracellular matrix in the lungs, as well as secrete chemokines that attract other immune cells such as monocytes and lymphocytes. In the latter population, the balance in COPD airways is tipped towards cytotoxic cell types such as CD8 + T cells [ 3 ] and NK cells [ 4 ]. Among regulatory immune cells, regulatory T cells (Tregs) are thought to be a key player, particularly in protecting the body from an over activated immune response [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Airway regulatory T cells are decreased in COPD with a rapid decline in lung function

et al. 2020

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Background Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1. Methods Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry. Results The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function. Conclusions COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1. Trial registration Clinicaltrials.gov identifier NCT02729220

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“…Airway damage in COPD is triggered by dust, fumes, vapors, or gas, but the primary factor is exposure to tobacco smoke ( 23 ). Cigarette smoke alters both innate and adaptive immunity by upregulating cytokines (IL-1, IL-6, IL-8, tumor necrosis factor [TNF]-α…) ( 24 , 25 ), and modifying the physiological function of alveolar macrophages ( 26 ), dendritic cells ( 27 ), neutrophils ( 28 ), and natural killer cells ( 29 ). Smoking also modifies the behavior of the epithelium by increasing mucin production (MUC5AC) ( 30 ) and disrupting epithelial cell-cell junctions, thus increasing the permeability of the epithelial barrier ( 31 ).…”

Section: Pathophysiology Of Asthma and Copdmentioning

confidence: 99%

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

et al. 2021

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Chronic respiratory diseases (CRDs) are an important factor of morbidity and mortality, accounting for approximately 6% of total deaths worldwide. The main CRDs are asthma and chronic obstructive pulmonary disease (COPD). These complex diseases have different triggers including allergens, pollutants, tobacco smoke, and other risk factors. It is important to highlight that although CRDs are incurable, various forms of treatment improve shortness of breath and quality of life. The search for tools that can ensure accurate diagnosis and treatment is crucial. MicroRNAs (miRNAs) are small non-coding RNAs and have been described as promising diagnostic and therapeutic biomarkers for CRDs. They are implicated in multiple processes of asthma and COPD, regulating pathways associated with inflammation, thereby showing that miRNAs are critical regulators of the immune response. Indeed, miRNAs have been found to be deregulated in several biofluids (sputum, bronchoalveolar lavage, and serum) and in both structural lung and immune cells of patients in comparison to healthy subjects, showing their potential role as biomarkers. Also, miRNAs play a part in the development or termination of histopathological changes and comorbidities, revealing the complexity of miRNA regulation and opening up new treatment possibilities. Finally, miRNAs have been proposed as prognostic tools in response to both conventional and biologic treatments for asthma or COPD, and miRNA-based treatment has emerged as a potential approach for clinical intervention in these respiratory diseases; however, this field is still in development. The present review applies a systems biology approach to the understanding of miRNA regulatory networks in asthma and COPD, summarizing their roles in pathophysiology, diagnosis, and treatment.

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Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking

Cited by 19 publications

References 30 publications

The Influence of Innate Lymphoid Cells and Unconventional T Cells in Chronic Inflammatory Lung Disease

The Influence of Innate Lymphoid Cells and Unconventional T Cells in Chronic Inflammatory Lung Disease

Airway regulatory T cells are decreased in COPD with a rapid decline in lung function

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

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