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Anti-viral responses of tissue-resident CD49a+ lung NK cells are dysregulated in COPD

Anti-viral responses of tissue-resident CD49a+ lung NK cells are dysregulated in COPD
Anti-viral responses of tissue-resident CD49a+ lung NK cells are dysregulated in COPD
Rationale: Tissue-resident natural killer cells have been identified in numerous organs, but little is known about their functional contribution to respiratory immunity, in particular during chronic lung diseases such as COPD.
Objectives: To investigate the phenotype and antiviral responses of trNK cells in murine cigarette smoke-induced experimental COPD and in human lung parenchyma from COPD donors.
Methods: Mice were exposed to cigarette smoke for 10 weeks to induce COPD-like lung disease. Lung tissue resident NK cell phenotypes and function were analysed by flow cytometry in both murine and human disease with and without challenge with influenza A virus.
Measurements and Main Results: In the mouse lung CD49a+CD49b+EOMES+ and CD49a+CD49b-EOMESlo NK cell populations had a distinct phenotype compared with CD49a- circulating NK cells. CD49a+ NK cells were more extensively altered earlier in disease onset than circulating NK cells and increased proportions of CD49a+ NK cells correlated with worsening disease in both murine and human COPD. Furthermore, the presence of lung disease delayed both circulating and tissue-resident NK cell functional responses to influenza infection. CD49a+ NK cells markedly increased their NKG2D, CD103 and CD69 expression in experimental COPD following influenza infection, and human CD49a+ NK cells were hyperactive to ex vivo influenza infection in COPD donors.
Conclusions: Collectively, these results demonstrate that tissue-resident NK cell function is altered in cigarette smoke-induced disease and suggests that smoke exposure may aberrantly prime tissue-resident NK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.
1073-449X
Cooper, Grace Elizabeth
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Mayall, Jemma
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Donovan, Chantal
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Haw, Tatt J.
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Budden, Kurtis F.
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Hansbro, Nicole G.
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Blomme, Evy E.
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Maes, Tania
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Kong, Chia Wei
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Horvat, Jay C.
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Khakoo, Salim I.
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Wilkinson, Tom MA
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Hansbro, Philip M.
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Staples, Karl J.
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Cooper, Grace Elizabeth
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Mayall, Jemma
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Donovan, Chantal
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Haw, Tatt J.
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Budden, Kurtis F.
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Hansbro, Nicole G.
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Blomme, Evy E.
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Maes, Tania
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Kong, Chia Wei
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Horvat, Jay C.
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Khakoo, Salim I.
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Wilkinson, Tom MA
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Hansbro, Philip M.
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Staples, Karl J.
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Cooper, Grace Elizabeth, Mayall, Jemma, Donovan, Chantal, Haw, Tatt J., Budden, Kurtis F., Hansbro, Nicole G., Blomme, Evy E., Maes, Tania, Kong, Chia Wei, Horvat, Jay C., Khakoo, Salim I., Wilkinson, Tom MA, Hansbro, Philip M. and Staples, Karl J. (2022) Anti-viral responses of tissue-resident CD49a+ lung NK cells are dysregulated in COPD. American Journal of Respiratory and Critical Care Medicine. (doi:10.1164/rccm.202205-0848OC).

Record type: Article

Abstract

Rationale: Tissue-resident natural killer cells have been identified in numerous organs, but little is known about their functional contribution to respiratory immunity, in particular during chronic lung diseases such as COPD.
Objectives: To investigate the phenotype and antiviral responses of trNK cells in murine cigarette smoke-induced experimental COPD and in human lung parenchyma from COPD donors.
Methods: Mice were exposed to cigarette smoke for 10 weeks to induce COPD-like lung disease. Lung tissue resident NK cell phenotypes and function were analysed by flow cytometry in both murine and human disease with and without challenge with influenza A virus.
Measurements and Main Results: In the mouse lung CD49a+CD49b+EOMES+ and CD49a+CD49b-EOMESlo NK cell populations had a distinct phenotype compared with CD49a- circulating NK cells. CD49a+ NK cells were more extensively altered earlier in disease onset than circulating NK cells and increased proportions of CD49a+ NK cells correlated with worsening disease in both murine and human COPD. Furthermore, the presence of lung disease delayed both circulating and tissue-resident NK cell functional responses to influenza infection. CD49a+ NK cells markedly increased their NKG2D, CD103 and CD69 expression in experimental COPD following influenza infection, and human CD49a+ NK cells were hyperactive to ex vivo influenza infection in COPD donors.
Conclusions: Collectively, these results demonstrate that tissue-resident NK cell function is altered in cigarette smoke-induced disease and suggests that smoke exposure may aberrantly prime tissue-resident NK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.

Text
CD49a+NKcellsinCOPD_AJRCCM_2022_resubmission+supplement3 - Accepted Manuscript
Restricted to Repository staff only until 25 September 2023.
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Accepted/In Press date: 25 September 2022
e-pub ahead of print date: 28 September 2022

Identifiers

Local EPrints ID: 470751
URI: http://eprints.soton.ac.uk/id/eprint/470751
ISSN: 1073-449X
PURE UUID: e451b2d8-4164-46eb-9077-d9ebdd9d29c2
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 19 Oct 2022 16:50
Last modified: 20 Oct 2022 01:39

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Contributors

Author: Grace Elizabeth Cooper
Author: Jemma Mayall
Author: Chantal Donovan
Author: Tatt J. Haw
Author: Kurtis F. Budden
Author: Nicole G. Hansbro
Author: Evy E. Blomme
Author: Tania Maes
Author: Chia Wei Kong
Author: Jay C. Horvat
Author: Salim I. Khakoo
Author: Philip M. Hansbro
Author: Karl J. Staples ORCID iD

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