Eosinophil-derived IL-13 promotes emphysema

Abstract

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.

Current developments and future directions in COPD

“…These highly concentrated areas of type 2 inflammation may drive specific tissue remodelling. Indeed, eosinophil derived IL-13 has been shown to induce matrix metalloproteinase (MMP)-12 production from alveolar macrophages causing alveolar destruction in mice [47]. The authors of this study also demonstrated increased MMP-12 levels in COPD patients with eosinophilic inflammation and emphysema.…”

Using correlative microscopy for studying and treatment of Mycoplasma infections of the ophtalmic mucosa

“…The superantigen Mycoplasma function that explains the different behaviors of the subjects examinated. In fact, the patients belonging to the group of alleged allergic who did not present with tear IgE [7] as shown in the statistical graphs showed a constant, presence of the Mycoplasma, this has generated a chronic latent-type in lammation that manages to mimic an allergic-type response [7,8]. From our study we can understand that Mycoplasma has a pivotal role in infections, in fact it is a co-factor in all the described infectious typologies, but in particular in allergic and alleged allergic cases, it creates a phenomenon of stimulation of the immune system [9][10][11][12].…”

Sputum Inflammometry to Manage Chronic Obstructive Pulmonary Disease Exacerbations: Beyond Guidelines

“…More recent studies regarding the role of eosinophils in COPD have revealed evidence that challenges the spectator theory. In murine models, lung matrix metalloprotease 12 (MMP-12), a key mediator in emphysematous alveolar destruction produced by macrophages, was found to be elevated 52 . The levels of MMP-12 correlated with the presence of activated eosinophils and their subsequent IL-13 release.…”