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

doi:10.1183/13993003.01291-2018

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

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Journal	The European respiratory journal
Volume	53
Issue number	5
DOIs	https://doi.org/10.1183/13993003.01291-2018
State	Published - May 1 2019

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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Doyle, A. D., Mukherjee, M., LeSuer, W. E., Bittner, T. B., Pasha, S. M., Frere, J. J., Neely, J. L., Kloeber, J. A., Shim, K. P., Ochkur, S. I., Ho, T., Svenningsen, S., Wright, B. L., Rank, M. A., Lee, J. J., Nair, P., & Jacobsen, E. A. (2019). Eosinophil-derived IL-13 promotes emphysema. The European respiratory journal, 53(5). https://doi.org/10.1183/13993003.01291-2018

Eosinophil-derived IL-13 promotes emphysema. / Doyle, Alfred D.; Mukherjee, Manali; LeSuer, William E.; Bittner, Tyler B.; Pasha, Saif M.; Frere, Justin J.; Neely, Joseph L.; Kloeber, Jake A.; Shim, Kelly P.; Ochkur, Sergei I.; Ho, Terence; Svenningsen, Sarah; Wright, Benjamin L.; Rank, Matthew A.; Lee, James J.; Nair, Parameswaran; Jacobsen, Elizabeth A.

In: The European respiratory journal, Vol. 53, No. 5, 01.05.2019.

Research output: Contribution to journal › Article › peer-review

Doyle, Alfred D. ; Mukherjee, Manali ; LeSuer, William E. ; Bittner, Tyler B. ; Pasha, Saif M. ; Frere, Justin J. ; Neely, Joseph L. ; Kloeber, Jake A. ; Shim, Kelly P. ; Ochkur, Sergei I. ; Ho, Terence ; Svenningsen, Sarah ; Wright, Benjamin L. ; Rank, Matthew A. ; Lee, James J. ; Nair, Parameswaran ; Jacobsen, Elizabeth A. / Eosinophil-derived IL-13 promotes emphysema. In: The European respiratory journal. 2019 ; Vol. 53, No. 5.

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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.",

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AU - Mukherjee, Manali

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AU - Pasha, Saif M.

AU - Frere, Justin J.

AU - Neely, Joseph L.

AU - Kloeber, Jake A.

AU - Shim, Kelly P.

AU - Ochkur, Sergei I.

AU - Ho, Terence

AU - Svenningsen, Sarah

AU - Wright, Benjamin L.

AU - Rank, Matthew A.

AU - Lee, James J.

AU - Nair, Parameswaran

AU - Jacobsen, Elizabeth A.

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AB - 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.

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