Tissue-resident natural killer (trNK) 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 chronic obstructive pulmonary disease (COPD). 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. Mice were exposed to cigarette smoke for 12 weeks to induce COPD-like lung disease. Lung trNK cell phenotypes and function were analyzed by flow cytometry in both murine and human disease with and without challenge with influenza A virus. In the mouse lung, CD49aCD49bEOMES and CD49aCD49bEOMES 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 trNK cell functional responses to influenza infection. CD49a NK cells markedly increased their NKG2D, CD103, and CD69 expression in experimental COPD after influenza infection, and human CD49a NK cells were hyperactive to influenza infection in COPD donors. Collectively, these results demonstrate that trNK cell function is altered in cigarette smoke-induced disease and suggests that smoke exposure may aberrantly prime trNK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.
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http://dx.doi.org/10.1164/rccm.202205-0848OC | DOI Listing |
J Exp Med
March 2025
Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
In this issue of JEM, Sparano et al. (https://doi.org/10.
View Article and Find Full Text PDFMucosal Immunol
December 2024
Microbiology and Immunology Department, Loyola University Health Science Campus, Maywood, IL, United States 60153. Electronic address:
The murine uterus contains three subsets of innate lymphoid cells (ILCs). Innate lymphoid cell type 1 (ILC1) and conventional natural killer (cNK) cells seed the uterus before puberty. Tissue-resident NK (trNK) cells emerge at puberty and vary in number during the estrous cycle.
View Article and Find Full Text PDFJ Exp Med
March 2025
Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechanisms that initiate, maintain, and regulate the conversion of NK cells into tissue-resident NK (trNK) cells are currently not well understood.
View Article and Find Full Text PDFElife
December 2024
Department of Oncology, University of Oxford, Oxford, United Kingdom.
The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success.
View Article and Find Full Text PDFTransl Cancer Res
October 2024
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Background: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is an increasingly common malignancy. We aimed to explore the immune heterogeneity of natural killer (NK) cells in HPV-positive HNSCC.
Methods: Single-cell RNA-sequencing (scRNA-seq) and bulk RNA-sequencing datasets of HPV-positive HNSCC data were obtained from the Gene Expression Omnibus (GEO) database.
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