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Published in: Respiratory Research 1/2020

01-12-2020 | Bronchiectasis | Research

Adaptive NKG2C+ natural killer cells are related to exacerbations and nutritional abnormalities in COPD patients

Authors: Sergi Pascual-Guardia, Michelle Ataya, Isabel Ramírez-Martínez, José Yélamos, Roberto Chalela, Salomé Bellido, Miguel López-Botet, Joaquim Gea

Published in: Respiratory Research | Issue 1/2020

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Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic and often progressive disorder with a heterogeneous presentation and frequent systemic manifestations. Several aspects like persistence in smoking habit, continuous exacerbations, alpha-1-antitrypsin deficiency and inflammatory-immune response, are involved in the pathophysiology and progression of the disease. However, the role of natural killer (NK) cells remains controversial. Otherwise, human cytomegalovirus (HCMV) infection has been reported to induce an adaptive differentiation and expansion of an NK cell subset which carries the CD94/NKG2C receptor, which may contribute to an upset immune defense. For these reasons, our objective is to assess the distribution of NK cells and their subset in COPD patients and some of its phenotypes.

Methods

Peripheral blood samples were obtained from 66 COPD patients. HCMV serology and the proportions of total NK cells and the NKG2C+ and NKG2A+ subsets were evaluated by flow cytometry. The NKG2C genotype was also assessed.

Results

Eighty-eight per cent of COPD patients were HCMV(+), and the proportions of total NK cells were higher in patients with severe-very severe airway obstruction than in those with only mild-moderate involvement. There were no differences in the proportions of NKG2C+ cells between controls and COPD, either among COPD patients classified by severity of the disease. However, the percentage of NKG2C+ cells were higher in COPD patients with frequent exacerbations than in occasional exacerbators, and higher in cases with reduced lean mass (Fat free mass index) than in those with normal nutritional status.

Conclusion

These results suggest a relationship between levels of NKG2C+ cells in COPD patients and clinical variables closely linked to a poor/worse prognosis.
Literature
1.
go back to reference Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Erratum to "global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary" [arch Bronconeumol. 2017;53:128-49]. Arch Bronconeumol. 2017;53(7):411–2.PubMedCrossRef Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Erratum to "global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary" [arch Bronconeumol. 2017;53:128-49]. Arch Bronconeumol. 2017;53(7):411–2.PubMedCrossRef
2.
go back to reference Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almagro P, Quintano JA, et al. Spanish guidelines for Management of Chronic Obstructive Pulmonary Disease (GesEPOC) 2017. Pharmacological treatment of stable phase. Arch Bronconeumol. 2017;53(6):324–35.PubMedCrossRef Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almagro P, Quintano JA, et al. Spanish guidelines for Management of Chronic Obstructive Pulmonary Disease (GesEPOC) 2017. Pharmacological treatment of stable phase. Arch Bronconeumol. 2017;53(6):324–35.PubMedCrossRef
3.
go back to reference Garcia-Aymerich J, Gomez FP, Benet M, Farrero E, Basagana X, Gayete A, et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax. 2011;66(5):430–7.PubMedCrossRef Garcia-Aymerich J, Gomez FP, Benet M, Farrero E, Basagana X, Gayete A, et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax. 2011;66(5):430–7.PubMedCrossRef
4.
go back to reference de-Torres JP, Marin JM. Differences between GesEPOC and GOLD in 2017. Arch Bronconeumol. 2017;53(6):295–6.PubMedCrossRef de-Torres JP, Marin JM. Differences between GesEPOC and GOLD in 2017. Arch Bronconeumol. 2017;53(6):295–6.PubMedCrossRef
5.
go back to reference Gea J, Sancho-Munoz A, Chalela R. Nutritional status and muscle dysfunction in chronic respiratory diseases: stable phase versus acute exacerbations. J Thorac Dis. 2018;10(Suppl 12):S1332–S54.PubMedPubMedCentralCrossRef Gea J, Sancho-Munoz A, Chalela R. Nutritional status and muscle dysfunction in chronic respiratory diseases: stable phase versus acute exacerbations. J Thorac Dis. 2018;10(Suppl 12):S1332–S54.PubMedPubMedCentralCrossRef
6.
go back to reference Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183–92.PubMedCrossRef Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183–92.PubMedCrossRef
7.
go back to reference Fairclough L, Urbanowicz RA, Corne J, Lamb JR. Killer cells in chronic obstructive pulmonary disease. Clin Sci (Lond). 2008;114(8):533–41.CrossRef Fairclough L, Urbanowicz RA, Corne J, Lamb JR. Killer cells in chronic obstructive pulmonary disease. Clin Sci (Lond). 2008;114(8):533–41.CrossRef
8.
go back to reference Hodge G, Mukaro V, Holmes M, Reynolds PN, Hodge S. Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway. Respirology. 2013;18(2):369–76.PubMedCrossRef Hodge G, Mukaro V, Holmes M, Reynolds PN, Hodge S. Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway. Respirology. 2013;18(2):369–76.PubMedCrossRef
10.
go back to reference Hodge S, Hodge G, Nairn J, Holmes M, Reynolds PN. Increased airway granzyme b and perforin in current and ex-smoking COPD subjects. COPD. 2006;3(4):179–87.PubMedCrossRef Hodge S, Hodge G, Nairn J, Holmes M, Reynolds PN. Increased airway granzyme b and perforin in current and ex-smoking COPD subjects. COPD. 2006;3(4):179–87.PubMedCrossRef
11.
go back to reference Suzuki M, Sze MA, Campbell JD, Brothers JF 2nd, Lenburg ME, McDonough JE, et al. The cellular and molecular determinants of emphysematous destruction in COPD. Sci Rep. 2017;7(1):9562.PubMedPubMedCentralCrossRef Suzuki M, Sze MA, Campbell JD, Brothers JF 2nd, Lenburg ME, McDonough JE, et al. The cellular and molecular determinants of emphysematous destruction in COPD. Sci Rep. 2017;7(1):9562.PubMedPubMedCentralCrossRef
12.
go back to reference Astegiano S, Sidoti F, Costa C, Ostorero A, Alotto D, Castagnoli C, et al. Human cytomegalovirus load in fresh and glycerolized skin grafts. New Microbiol. 2010;33(3):253–6.PubMed Astegiano S, Sidoti F, Costa C, Ostorero A, Alotto D, Castagnoli C, et al. Human cytomegalovirus load in fresh and glycerolized skin grafts. New Microbiol. 2010;33(3):253–6.PubMed
13.
14.
go back to reference Tan DB, Amran FS, Teo TH, Price P, Moodley YP. Levels of CMV-reactive antibodies correlate with the induction of CD28(null) T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD). Cell Mol Immunol. 2016;13(4):551–3.PubMedCrossRef Tan DB, Amran FS, Teo TH, Price P, Moodley YP. Levels of CMV-reactive antibodies correlate with the induction of CD28(null) T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD). Cell Mol Immunol. 2016;13(4):551–3.PubMedCrossRef
15.
go back to reference Poole E, Juss JK, Krishna B, Herre J, Chilvers ER, Sinclair J. Alveolar macrophages isolated directly from human Cytomegalovirus (HCMV)-seropositive individuals are sites of HCMV reactivation in vivo. J Infect Dis. 2015;211(12):1936–42.PubMedCrossRef Poole E, Juss JK, Krishna B, Herre J, Chilvers ER, Sinclair J. Alveolar macrophages isolated directly from human Cytomegalovirus (HCMV)-seropositive individuals are sites of HCMV reactivation in vivo. J Infect Dis. 2015;211(12):1936–42.PubMedCrossRef
16.
go back to reference Lopez-Botet M, Muntasell A, Vilches C. The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Semin Immunol. 2014;26(2):145–51.CrossRef Lopez-Botet M, Muntasell A, Vilches C. The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Semin Immunol. 2014;26(2):145–51.CrossRef
17.
go back to reference Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol. 1999;17:189–220.PubMedCrossRef Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol. 1999;17:189–220.PubMedCrossRef
18.
go back to reference Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004;104(12):3664–71.PubMedCrossRef Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004;104(12):3664–71.PubMedCrossRef
19.
go back to reference Redondo-Pachon D, Crespo M, Yelamos J, Muntasell A, Perez-Saez MJ, Perez-Fernandez S, et al. Adaptive NKG2C+ NK cell response and the risk of Cytomegalovirus infection in kidney transplant recipients. J Immunol. 2017;198(1):94–101.PubMedCrossRef Redondo-Pachon D, Crespo M, Yelamos J, Muntasell A, Perez-Saez MJ, Perez-Fernandez S, et al. Adaptive NKG2C+ NK cell response and the risk of Cytomegalovirus infection in kidney transplant recipients. J Immunol. 2017;198(1):94–101.PubMedCrossRef
20.
go back to reference Muntasell A, Lopez-Montanes M, Vera A, Heredia G, Romo N, Penafiel J, et al. NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus. Eur J Immunol. 2013;43(12):3268–78.PubMedCrossRef Muntasell A, Lopez-Montanes M, Vera A, Heredia G, Romo N, Penafiel J, et al. NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus. Eur J Immunol. 2013;43(12):3268–78.PubMedCrossRef
21.
go back to reference Noble BJ. Clinical applications of perceived exertion. Med Sci Sports Exerc. 1982;14(5):406–11.PubMed Noble BJ. Clinical applications of perceived exertion. Med Sci Sports Exerc. 1982;14(5):406–11.PubMed
22.
go back to reference Mahler DA, Rosiello RA, Harver A, Lentine T, McGovern JF, Daubenspeck JA. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis. 1987;135(6):1229–33.PubMedCrossRef Mahler DA, Rosiello RA, Harver A, Lentine T, McGovern JF, Daubenspeck JA. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis. 1987;135(6):1229–33.PubMedCrossRef
23.
go back to reference Roca J, Sanchis J, Agusti-Vidal A, Segarra F, Navajas D, Rodriguez-Roisin R, et al. Spirometric reference values from a Mediterranean population. Bull Eur Physiopathol Respir. 1986;22(3):217–24.PubMed Roca J, Sanchis J, Agusti-Vidal A, Segarra F, Navajas D, Rodriguez-Roisin R, et al. Spirometric reference values from a Mediterranean population. Bull Eur Physiopathol Respir. 1986;22(3):217–24.PubMed
24.
go back to reference Roca J, Rodriguez-Roisin R, Cobo E, Burgos F, Perez J, Clausen JL. Single-breath carbon monoxide diffusing capacity prediction equations from a Mediterranean population. Am Rev Respir Dis. 1990;141(4 Pt 1):1026–32.PubMedCrossRef Roca J, Rodriguez-Roisin R, Cobo E, Burgos F, Perez J, Clausen JL. Single-breath carbon monoxide diffusing capacity prediction equations from a Mediterranean population. Am Rev Respir Dis. 1990;141(4 Pt 1):1026–32.PubMedCrossRef
25.
go back to reference Roca J, Burgos F, Barbera JA, Sunyer J, Rodriguez-Roisin R, Castellsague J, et al. Prediction equations for plethysmographic lung volumes. Respir Med. 1998;92(3):454–60.PubMedCrossRef Roca J, Burgos F, Barbera JA, Sunyer J, Rodriguez-Roisin R, Castellsague J, et al. Prediction equations for plethysmographic lung volumes. Respir Med. 1998;92(3):454–60.PubMedCrossRef
26.
go back to reference Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(6 Pt 1):1791–7.PubMedCrossRef Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(6 Pt 1):1791–7.PubMedCrossRef
27.
go back to reference Crespo M, Yelamos J, Redondo D, Muntasell A, Perez-Saez MJ, Lopez-Montanes M, et al. Circulating NK-cell subsets in renal allograft recipients with anti-HLA donor-specific antibodies. Am J Transplant. 2015;15(3):806–14.PubMedCrossRef Crespo M, Yelamos J, Redondo D, Muntasell A, Perez-Saez MJ, Lopez-Montanes M, et al. Circulating NK-cell subsets in renal allograft recipients with anti-HLA donor-specific antibodies. Am J Transplant. 2015;15(3):806–14.PubMedCrossRef
28.
go back to reference Moraru M, Canizares M, Muntasell A, de Pablo R, Lopez-Botet M, Vilches C. Assessment of copy-number variation in the NKG2C receptor gene in a single-tube and characterization of a reference cell panel, using standard polymerase chain reaction. Tissue Antigens. 2012;80(2):184–7.PubMedCrossRef Moraru M, Canizares M, Muntasell A, de Pablo R, Lopez-Botet M, Vilches C. Assessment of copy-number variation in the NKG2C receptor gene in a single-tube and characterization of a reference cell panel, using standard polymerase chain reaction. Tissue Antigens. 2012;80(2):184–7.PubMedCrossRef
29.
go back to reference Phan MT, Chun S, Kim SH, Ali AK, Lee SH, Kim S, et al. Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population: reference range, influence of age and sex, and correlation between NK cell receptors and cytotoxicity. Hum Immunol. 2017;78(2):103–12.PubMedCrossRef Phan MT, Chun S, Kim SH, Ali AK, Lee SH, Kim S, et al. Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population: reference range, influence of age and sex, and correlation between NK cell receptors and cytotoxicity. Hum Immunol. 2017;78(2):103–12.PubMedCrossRef
30.
go back to reference Robles C, Casabonne D, Benavente Y, Costas L, Gonzalez-Barca E, Aymerich M, et al. Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study. J Gen Virol. 2015;96(8):2286–92.PubMedCrossRef Robles C, Casabonne D, Benavente Y, Costas L, Gonzalez-Barca E, Aymerich M, et al. Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study. J Gen Virol. 2015;96(8):2286–92.PubMedCrossRef
31.
go back to reference Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.PubMedCrossRef Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.PubMedCrossRef
32.
go back to reference Holder KA, Grant MD. Human cytomegalovirus IL-10 augments NK cell cytotoxicity. J Leukoc Biol. 2019;106(2):447–454.PubMedCrossRef Holder KA, Grant MD. Human cytomegalovirus IL-10 augments NK cell cytotoxicity. J Leukoc Biol. 2019;106(2):447–454.PubMedCrossRef
33.
go back to reference Lopez-Botet M, Muntasell A, Martinez-Rodriguez JE, Lopez-Montanes M, Costa-Garcia M, Pupuleku A. Development of the adaptive NK cell response to human cytomegalovirus in the context of aging. Mech Ageing Dev. 2016;158:23–6.PubMedCrossRef Lopez-Botet M, Muntasell A, Martinez-Rodriguez JE, Lopez-Montanes M, Costa-Garcia M, Pupuleku A. Development of the adaptive NK cell response to human cytomegalovirus in the context of aging. Mech Ageing Dev. 2016;158:23–6.PubMedCrossRef
34.
go back to reference Costabel U, Maier K, Teschler H, Wang YM. Local immune components in chronic obstructive pulmonary disease. Respir. 1992;59(Suppl 1):17–9.CrossRef Costabel U, Maier K, Teschler H, Wang YM. Local immune components in chronic obstructive pulmonary disease. Respir. 1992;59(Suppl 1):17–9.CrossRef
35.
go back to reference Urbanowicz RA, Lamb JR, Todd I, Corne JM, Fairclough LC. Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients. Respir Res. 2010;11:76.PubMedPubMedCentralCrossRef Urbanowicz RA, Lamb JR, Todd I, Corne JM, Fairclough LC. Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients. Respir Res. 2010;11:76.PubMedPubMedCentralCrossRef
36.
go back to reference Tang Y, Li X, Wang M, Zou Q, Zhao S, Sun B, et al. Increased numbers of NK cells, NKT-like cells, and NK inhibitory receptors in peripheral blood of patients with chronic obstructive pulmonary disease. Clin Dev Immunol. 2013;2013:721782.PubMedPubMedCentral Tang Y, Li X, Wang M, Zou Q, Zhao S, Sun B, et al. Increased numbers of NK cells, NKT-like cells, and NK inhibitory receptors in peripheral blood of patients with chronic obstructive pulmonary disease. Clin Dev Immunol. 2013;2013:721782.PubMedPubMedCentral
37.
go back to reference Folli C, Chiappori A, Pellegrini M, Garelli V, Riccio AM, De Ferrari L, et al. COPD treatment: real life and experimental effects on peripheral NK cells, their receptors expression and their IFN-gamma secretion. Pulm Pharmacol Ther. 2012;25(5):371–6.PubMedCrossRef Folli C, Chiappori A, Pellegrini M, Garelli V, Riccio AM, De Ferrari L, et al. COPD treatment: real life and experimental effects on peripheral NK cells, their receptors expression and their IFN-gamma secretion. Pulm Pharmacol Ther. 2012;25(5):371–6.PubMedCrossRef
38.
go back to reference Prieto A, Reyes E, Bernstein ED, Martinez B, Monserrat J, Izquierdo JL, et al. Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferon). Am J Respir Crit Care Med. 2001;163(7):1578–83.PubMedCrossRef Prieto A, Reyes E, Bernstein ED, Martinez B, Monserrat J, Izquierdo JL, et al. Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferon). Am J Respir Crit Care Med. 2001;163(7):1578–83.PubMedCrossRef
39.
40.
go back to reference Wang J, Urbanowicz RA, Tighe PJ, Todd I, Corne JM, Fairclough LC. Differential activation of killer cells in the circulation and the lung: a study of current smoking status and chronic obstructive pulmonary disease (COPD). PLoS One. 2013;8(3):e58556.PubMedPubMedCentralCrossRef Wang J, Urbanowicz RA, Tighe PJ, Todd I, Corne JM, Fairclough LC. Differential activation of killer cells in the circulation and the lung: a study of current smoking status and chronic obstructive pulmonary disease (COPD). PLoS One. 2013;8(3):e58556.PubMedPubMedCentralCrossRef
41.
42.
go back to reference Finch DK, Stolberg VR, Ferguson J, Alikaj H, Kady MR, Richmond BW, et al. Lung dendritic cells drive natural killer cytotoxicity in chronic obstructive pulmonary disease via IL-15Ralpha. Am J Respir Crit Care Med. 2018;198(9):1140–50.PubMedPubMedCentralCrossRef Finch DK, Stolberg VR, Ferguson J, Alikaj H, Kady MR, Richmond BW, et al. Lung dendritic cells drive natural killer cytotoxicity in chronic obstructive pulmonary disease via IL-15Ralpha. Am J Respir Crit Care Med. 2018;198(9):1140–50.PubMedPubMedCentralCrossRef
43.
go back to reference Freeman CM, Stolberg VR, Crudgington S, Martinez FJ, Han MK, Chensue SW, et al. Human CD56+ cytotoxic lung lymphocytes kill autologous lung cells in chronic obstructive pulmonary disease. PLoS One. 2014;9(7):e103840.PubMedPubMedCentralCrossRef Freeman CM, Stolberg VR, Crudgington S, Martinez FJ, Han MK, Chensue SW, et al. Human CD56+ cytotoxic lung lymphocytes kill autologous lung cells in chronic obstructive pulmonary disease. PLoS One. 2014;9(7):e103840.PubMedPubMedCentralCrossRef
44.
go back to reference Boyton RJ, Smith J, Ward R, Jones M, Ozerovitch L, Wilson R, et al. HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis. Am J Respir Crit Care Med. 2006;173(3):327–33.PubMedCrossRef Boyton RJ, Smith J, Ward R, Jones M, Ozerovitch L, Wilson R, et al. HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis. Am J Respir Crit Care Med. 2006;173(3):327–33.PubMedCrossRef
45.
go back to reference Boyton RJ, Altmann DM. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol. 2007;149(1):1–8.PubMedPubMedCentralCrossRef Boyton RJ, Altmann DM. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol. 2007;149(1):1–8.PubMedPubMedCentralCrossRef
46.
47.
go back to reference Motz GT, Eppert BL, Wortham BW, Amos-Kroohs RM, Flury JL, Wesselkamper SC, et al. Chronic cigarette smoke exposure primes NK cell activation in a mouse model of chronic obstructive pulmonary disease. J Immunol. 2010;184(8):4460–9.PubMedCrossRef Motz GT, Eppert BL, Wortham BW, Amos-Kroohs RM, Flury JL, Wesselkamper SC, et al. Chronic cigarette smoke exposure primes NK cell activation in a mouse model of chronic obstructive pulmonary disease. J Immunol. 2010;184(8):4460–9.PubMedCrossRef
48.
go back to reference Morrow JD, Qiu W, Chhabra D, Rennard SI, Belloni P, Belousov A, et al. Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods. BMC Med Genet. 2015;8:1. Morrow JD, Qiu W, Chhabra D, Rennard SI, Belloni P, Belousov A, et al. Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods. BMC Med Genet. 2015;8:1.
49.
go back to reference Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med. 2011;105(Suppl 1):S20–5.PubMedCrossRef Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med. 2011;105(Suppl 1):S20–5.PubMedCrossRef
50.
go back to reference Hodge G, Holmes M, Jersmann H, Reynolds PN, Hodge S. Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD. BMC Pulm Med. 2014;14:85.PubMedPubMedCentralCrossRef Hodge G, Holmes M, Jersmann H, Reynolds PN, Hodge S. Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD. BMC Pulm Med. 2014;14:85.PubMedPubMedCentralCrossRef
51.
go back to reference Roos-Engstrand E, Pourazar J, Behndig AF, Blomberg A, Bucht A. Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD. Respir Res. 2010;11:128.PubMedPubMedCentralCrossRef Roos-Engstrand E, Pourazar J, Behndig AF, Blomberg A, Bucht A. Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD. Respir Res. 2010;11:128.PubMedPubMedCentralCrossRef
52.
go back to reference Borchers MT, Wesselkamper SC, Curull V, Ramirez-Sarmiento A, Sanchez-Font A, Garcia-Aymerich J, et al. Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease. J Clin Invest. 2009;119(3):636–49.PubMedPubMedCentralCrossRef Borchers MT, Wesselkamper SC, Curull V, Ramirez-Sarmiento A, Sanchez-Font A, Garcia-Aymerich J, et al. Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease. J Clin Invest. 2009;119(3):636–49.PubMedPubMedCentralCrossRef
53.
go back to reference Wortham BW, Eppert BL, Motz GT, Flury JL, Orozco-Levi M, Hoebe K, et al. NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease. J Immunol. 2012;188(9):4468–75.PubMedPubMedCentralCrossRef Wortham BW, Eppert BL, Motz GT, Flury JL, Orozco-Levi M, Hoebe K, et al. NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease. J Immunol. 2012;188(9):4468–75.PubMedPubMedCentralCrossRef
54.
go back to reference Soderberg-Naucler C, Streblow DN, Fish KN, Allan-Yorke J, Smith PP, Nelson JA. Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J Virol. 2001;75(16):7543–54.PubMedPubMedCentralCrossRef Soderberg-Naucler C, Streblow DN, Fish KN, Allan-Yorke J, Smith PP, Nelson JA. Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J Virol. 2001;75(16):7543–54.PubMedPubMedCentralCrossRef
55.
go back to reference Soderberg-Naucler C, Fish KN, Nelson JA. Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines. J Clin Invest. 1997;100(12):3154–63.PubMedPubMedCentralCrossRef Soderberg-Naucler C, Fish KN, Nelson JA. Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines. J Clin Invest. 1997;100(12):3154–63.PubMedPubMedCentralCrossRef
56.
go back to reference Forte E, Swaminathan S, Schroeder MW, Kim JY, Terhune SS, Hummel M. Tumor Necrosis Factor Alpha Induces Reactivation of Human Cytomegalovirus Independently of Myeloid Cell Differentiation following Posttranscriptional Establishment of Latency. MBio. 2018;9(5). Forte E, Swaminathan S, Schroeder MW, Kim JY, Terhune SS, Hummel M. Tumor Necrosis Factor Alpha Induces Reactivation of Human Cytomegalovirus Independently of Myeloid Cell Differentiation following Posttranscriptional Establishment of Latency. MBio. 2018;9(5).
Metadata
Title
Adaptive NKG2C+ natural killer cells are related to exacerbations and nutritional abnormalities in COPD patients
Authors
Sergi Pascual-Guardia
Michelle Ataya
Isabel Ramírez-Martínez
José Yélamos
Roberto Chalela
Salomé Bellido
Miguel López-Botet
Joaquim Gea
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-1323-4

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