Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease

Osterburg, Andrew R.; Lach, Laura; Panos, Ralph J.; Borchers, Michael T.

doi:10.1038/s41598-020-58326-7

Cited by 14 publications

(21 citation statements)

References 33 publications

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“…The present findings are also concordant with studies that implicate NK cells in COPD pathogenesis (7,(26)(27)(28). Although most previous reports find minimal differences of NK cell counts in peripheral blood of COPD patients compared to controls (see also Figure 4) (29,30), subtle phenotypic alterations that associate with disease manifestations have also been described (26).…”

Section: Discussionsupporting

confidence: 93%

HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk

et al. 2021

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A role for hereditary influences in the susceptibility for chronic obstructive pulmonary disease (COPD) is widely recognized. Cytotoxic lymphocytes are implicated in COPD pathogenesis, and functions of these leukocytes are modulated by interactions between their killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA)-Class I molecules on target cells. We hypothesized HLA-Class I and KIR inheritance affect risks for COPD. HLA-Class I alleles and KIR genotypes were defined by candidate gene analyses in multiple cohorts of COPD patients (total n=392) and control smokers with normal spirometry (total n=342). Compared to controls, COPD patients had over-representations of HLA-C*07 and activating KIR2DS1, with under-representations of HLA-C*12. Particular HLA-KIR permutations were synergistic; e.g. the presence of HLA-C*07 + KIR2DS1 + HLA-C12 null vs. HLAC*07 null + KIR2DS1 null + HLA-C12 was associated with COPD, especially among HLA-C1 allotype homozygotes (OR=18.5, 95%CI=3.7-90.9, p<0.0001). Cytotoxicity of COPD lymphocytes was more enhanced by KIR stimulation than those of controls (p=0.005) and was correlated with lung function (r=0.44, p=0.004). These data show HLA-C and KIR polymorphisms strongly influence COPD susceptibility and highlight the importance of lymphocyte-mediated cytotoxicity in COPD pathogenesis. Findings here also indicate HLA-KIR typing could stratify at-risk patients and raise possibilities HLA-KIR axis modulation may have therapeutic potential.

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Section: Discussionsupporting

confidence: 93%

HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk

et al. 2021

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“…It is characterized by airflow obstruction, emphysema, recurrent infections (24,39), chronic inflammation, and overproduction of mucus (40). Acute exacerbations significantly limit the quality of life of the patients (38,39). The exacerbations are in principle caused by viral or bacterial infections, the latter most frequently due to Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis (39).…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

“…Recently, Osterburg et al presented a multiparameter flow cytometry study of PB NK cells from COPD patients compared with smokers and never smokers (38). In contrast to those, COPD patients and smokers highly expressed the maturation marker CD57 as well as the AR NKp46 and NKp44 (normally only present on activated but not on baseline NK cells), but lower levels of CD56.…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

“…In contrast to those, COPD patients and smokers highly expressed the maturation marker CD57 as well as the AR NKp46 and NKp44 (normally only present on activated but not on baseline NK cells), but lower levels of CD56. Certain NK cell subpopulations were indicative of prior exacerbations (38).…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

“…This entity is the third cause of mortality in the United States of America ( 3 ) and worldwide ( 38 ) and is in most cases the consequence of prolonged cigarette smoking ( 39 ). It is characterized by airflow obstruction, emphysema, recurrent infections ( 24 , 39 ), chronic inflammation, and overproduction of mucus ( 40 ).…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

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Airway Natural Killer Cells and Bacteria in Health and Disease

2020

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Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field.

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