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

Chantal Donovan, Malcolm R. Starkey, Richard Y. Kim, Batika M.J. Rana, Jillian L. Barlow, Bernadette Jones, Tatt Jhong Haw, Prema Mono Nair, Kurtis Budden, Guy J.M. Cameron, Jay C. Horvat, Peter A. Wark, Paul S. Foster, Andrew N.J. McKenzie, Philip M. Hansbro

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22 Citations (Scopus)

Abstract

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 Rora fl/fl Il7r Cre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1 −/− , and Rora fl/fl Il7r Cre 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 Rora fl/fl Il7r Cre 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.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalJournal of leukocyte biology
Volume105
Issue number1
DOIs
Publication statusPublished - Jan 2019
Externally publishedYes

Keywords

  • COPD
  • emphysema
  • ILC2s
  • inflammation
  • remodelling
  • T cells

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