Abstract
Objectives: Innate lymphoid cells (ILCs) secrete cytokines, such as IFN-γ, IL-13 and IL-17, which are linked to chronic obstructive pulmonary disease (COPD). Here, we investigated the role of pulmonary ILCs in COPD pathogenesis. Methods: Lung ILC subsets in COPD and control subjects were quantified using flow cytometry and associated with clinical parameters. Tissue localisation of ILC and T-cell subsets was determined by immunohistochemistry. Mice were exposed to air or cigarette smoke (CS) for 1, 4 or 24 weeks to investigate whether pulmonary ILC numbers and activation are altered and whether they contribute to CS-induced innate inflammatory responses. Results: Quantification of lung ILC subsets demonstrated that ILC1 frequency in the total ILC population was elevated in COPD and was associated with smoking and severity of respiratory symptoms (COPD Assessment Test [CAT] score). All three ILC subsets localised near lymphoid aggregates in COPD. In the COPD mouse model, CS exposure in C57BL/6J mice increased ILC numbers at all time points, with relative increases in ILC1 in bronchoalveolar lavage (BAL) fluid. Importantly, CS exposure induced increases in neutrophils, monocytes and dendritic cells that remained elevated in Rag2/Il2rg-deficient mice that lack adaptive immune cells and ILCs. However, CS-induced CXCL1, IL-6, TNF-α and IFN-γ levels were reduced by ILC deficiency. Conclusion: The ILC1 subset is increased in COPD patients and correlates with smoking and severity of respiratory symptoms. ILCs also increase upon CS exposure in C57BL/6J mice. In the absence of adaptive immunity, ILCs contribute to CS-induced pro-inflammatory mediator release, but are redundant in CS-induced innate inflammation.
| Original language | English |
|---|---|
| Article number | e1287 |
| Journal | Clinical and Translational Immunology |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:The research described here was supported by the Fund for Scientific Research in Flanders (FWO Vlaanderen, G053516N); FWO-EOS Project G0G2318N; and a Ghent University Grant (BOF19-GOA-008). The work of Sara Wijnant was funded by the Funds for Scientific Research Flanders (FWO Vlaanderen, 3G037618). EEB received an FWO Grant for a long stay abroad, which supported her research project in the Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle. MB received an ERS short-term research training fellowship 2015-2016, which supported his internship in the Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent. PMH is funded by a fellowship from the NHMRC (1175134) and by UTS. TM reports grants from Ghent University, grants from Fund for Scientific Research in Flanders, during the conduct of the study, and holds a Chiesi Chair on Environmental factors in asthma. The authors thank Ann Neesen, Indra De Borle, Katleen De Saedeleer, Anouck Goethals and Greet Barbier from the Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine (Ghent University Hospital, Ghent, Belgium) for excellent technical assistance.
Funding Information:
The research described here was supported by the Fund for Scientific Research in Flanders (FWO Vlaanderen, G053516N); FWO‐EOS Project G0G2318N; and a Ghent University Grant (BOF19‐GOA‐008). The work of Sara Wijnant was funded by the Funds for Scientific Research Flanders (FWO Vlaanderen, 3G037618). EEB received an FWO Grant for a long stay abroad, which supported her research project in the Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle. MB received an ERS short‐term research training fellowship 2015‐2016, which supported his internship in the Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent. PMH is funded by a fellowship from the NHMRC (1175134) and by UTS. TM reports grants from Ghent University, grants from Fund for Scientific Research in Flanders, during the conduct of the study, and holds a Chiesi Chair on Environmental factors in asthma. The authors thank Ann Neesen, Indra De Borle, Katleen De Saedeleer, Anouck Goethals and Greet Barbier from the Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine (Ghent University Hospital, Ghent, Belgium) for excellent technical assistance.
Publisher Copyright:
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.