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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Chantal Donovan¹  Malcolm R. Starkey¹  Richard Y. Kim¹  Batika M. J. Rana²  Jillian L. Barlow²  Bernadette Jones¹  Tatt Jhong Haw¹  Prema Mono Nair¹  Kurtis Budden¹  Guy J.M. Cameron¹  Jay C. Horvat¹  Peter A. Wark¹  Paul S. Foster¹  Andrew N. J. McKenzie²  Philip M. Hansbro¹ 

[1] 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

关键词: COPD;    emphysema;    ILC2s;    inflammation;    remodelling;    T cells;   

DOI  :  10.1002/JLB.3AB0518-178R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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/flIl7r^Cre [ILC2‐deficient] mice). Wild‐type (WT) C57BL/6 mice, Rag1^−/−, and Rora^fl/flIl7r^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/flIl7r^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.

【 授权许可】

CC BY