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J Leukoc Biol. 2018 Sep 27. doi: 10.1002/JLB.3AB0518-178R. [Epub ahead of print]

Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease.

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Priority Research Centres for Healthy Lungs and GrowUpWell, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK.
The Centenary Institute and the School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.


Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1-/- and Rorafl/fl Il7rCre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1-/- , and Rorafl/fl Il7rCre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12 weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed. WT, Rag1-/- , and ILC2-deficient mice exposed to CS had similar levels of airway inflammation and impaired lung function. CS exposure increased small airway collagen deposition in WT mice. Rag1-/- normal air- and CS-exposed mice had significantly increased collagen deposition compared to similarly exposed WT mice, which was associated with increases in IL-33, IL-13, and ILC2 numbers. CS-exposed Rorafl/fl Il7rCre mice were protected from emphysema, but had increased IL-33/IL-13 expression and collagen deposition compared to WT CS-exposed mice. T/B lymphocytes and ILC2s play roles in airway collagen deposition/fibrosis, but not inflammation, in experimental COPD.


COPD; ILC2s; T cells; emphysema; inflammation; remodelling


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