@article{d8f5bc2856594f0f98e0f8132ba5e33e,
title = "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.",
author = "Doyle, {Alfred D.} and Manali Mukherjee and LeSuer, {William E.} and Bittner, {Tyler B.} and Pasha, {Saif M.} and Frere, {Justin J.} and Neely, {Joseph L.} and Kloeber, {Jake A.} and Shim, {Kelly P.} and Ochkur, {Sergei I.} and Terence Ho and Sarah Svenningsen and Wright, {Benjamin L.} and Rank, {Matthew A.} and Lee, {James J.} and Parameswaran Nair and Jacobsen, {Elizabeth A.}",
note = "Funding Information: Support statement: This work was supported by Mayo Foundation for Medical Education and Research, NIH NHLBI R01 HL058723 and HL065228, and NIH NCRR K26 RR0109709. A.D. Doyle was supported by the Mayo Graduate School, the Mayo Clinic Sidney Luckman Family Predoctoral Fellowship, the Donald R. Levin Family Foundation and NIH NHLBI F31HL124959. P. Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: Conflict of interest: A.D. Doyle reports grants from NIH (F31HL124959), donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, and a scholarship at the Mayo Clinic from Mayo Clinic Sidney Luckman Family Predoctoral Fellowship, during the conduct of the study. M. Mukherjee has nothing to disclose. W.E. LeSuer has nothing to disclose. T.B. Bittner has nothing to disclose. S.M. Pasha has nothing to disclose. J.J. Frere has nothing to disclose. J.L. Neely has nothing to disclose. J.A. Kloeber has nothing to disclose. K.P. Shim has nothing to disclose. S.I. Ochkur has nothing to disclose. T. Ho has nothing to disclose. S. Svenningsen has nothing to disclose. B.L. Wright reports donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, during the conduct of the study. M.A. Rank has nothing to disclose. J.J. Lee received grants from NIH (HL058723), NIH NCRR (K26 RR0109709) and the Mayo Foundation for Medical Education and Research, during the conduct of this study; J.J. Lee is deceased and this statement was made on behalf of the author by the corresponding author. P. Nair reports grants and personal fees for consultancy and lecturing from AstraZeneca and Teva, grants from Boehringer Ingelheim, grants and personal fees for lecturing from Novartis, grants and personal fees for consultancy from Sanofi and GSK, and personal fees for consultancy from Theravance and Knopp, outside the submitted work. E.A. Jacobsen reports grants from NIH (HL065228), and donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, during the conduct of the study. Publisher Copyright: Copyright {\textcopyright} ERS 2019",
year = "2019",
month = may,
day = "1",
doi = "10.1183/13993003.01291-2018",
language = "English (US)",
volume = "53",
journal = "European Respiratory Journal",
issn = "0903-1936",
number = "5",
}