Eosinophil-derived IL-13 promotes emphysema

Eur Respir J. 2019 May 30;53(5):1801291. doi: 10.1183/13993003.01291-2018. Print 2019 May.


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 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Asthma / immunology
  • Asthma / pathology
  • Disease Models, Animal
  • Eosinophils / immunology*
  • Eosinophils / pathology
  • Female
  • Humans
  • Interleukin-13 / immunology*
  • Interleukin-4 / immunology
  • Macrophages, Alveolar / pathology
  • Male
  • Matrix Metalloproteinase 12 / immunology
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Multivariate Analysis
  • Pneumonia / etiology*
  • Pneumonia / immunology
  • Pneumonia / pathology
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / etiology*
  • Pulmonary Emphysema / immunology
  • Pulmonary Emphysema / pathology
  • Regression Analysis
  • Respiratory System / physiopathology


  • Interleukin-13
  • Interleukin-4
  • MMP12 protein, human
  • Matrix Metalloproteinase 12