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

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.

More information

Identifiers

ORCID for Chia Wei Kong: orcid.org/0000-0002-8260-6967

ORCID for Salim I. Khakoo: orcid.org/0000-0002-4057-9091

ORCID for Karl J. Staples: orcid.org/0000-0003-3844-6457

Catalogue record

Export record

Altmetrics