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 Wright, Matthew A Rank, James J. Lee, Parameswaran Nair, Elizabeth A. Jacobsen

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalThe European respiratory journal
Volume53
Issue number5
DOIs
StatePublished - May 1 2019

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Interleukin-13
Emphysema
Metalloproteases
Eosinophils
Eosinophilia
Chronic Disease
Sputum
Interleukin-4
Chronic Obstructive Pulmonary Disease
Pneumonia
Lung
Forced Expiratory Volume
Alveolar Macrophages
Bronchoalveolar Lavage
Transgenic Mice
Asthma
Tomography
Pathology

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Doyle, A. D., Mukherjee, M., LeSuer, W. E., Bittner, T. B., Pasha, S. M., Frere, J. J., ... 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; 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 journalArticle

Doyle, AD, Mukherjee, M, LeSuer, WE, Bittner, TB, Pasha, SM, Frere, JJ, Neely, JL, Kloeber, JA, Shim, KP, Ochkur, SI, Ho, T, Svenningsen, S, Wright, B, Rank, MA, Lee, JJ, Nair, P & Jacobsen, EA 2019, 'Eosinophil-derived IL-13 promotes emphysema', The European respiratory journal, vol. 53, no. 5. https://doi.org/10.1183/13993003.01291-2018
Doyle AD, Mukherjee M, LeSuer WE, Bittner TB, Pasha SM, Frere JJ et al. Eosinophil-derived IL-13 promotes emphysema. The European respiratory journal. 2019 May 1;53(5). https://doi.org/10.1183/13993003.01291-2018
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 ; 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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AU - Doyle, Alfred D.

AU - Mukherjee, Manali

AU - LeSuer, William E.

AU - Bittner, Tyler B.

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

AU - Rank, Matthew A

AU - Lee, James J.

AU - Nair, Parameswaran

AU - Jacobsen, Elizabeth A.

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N2 - 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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