Eosinophil-derived IL-13 promotes emphysema

Alfred D Doyle, Manali Mukherjee, William E LeSuer, Tyler B Bittner, Saif M Pasha, Justin J Frere, Joseph L Neely, Jake A Kloeber, Kelly P Shim, Sergei I Ochkur, Terence Ho, Sarah Svenningsen, Benjamin L Wright, Matthew A Rank, James J Lee, Parameswaran Nair, Elizabeth A Jacobsen

European Respiratory Journal, 53(5), 1801291. 01/05/2019

PMID: 30728205


The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 …