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IL11 negatively impacts adult lung alveolar organoid formation

Rosa K. Kortekaas, Janette K. Burgess, Megan Webster, Reinoud Gosens
European Respiratory Journal 2021 58: PA2050; DOI: 10.1183/13993003.congress-2021.PA2050
Rosa K. Kortekaas
1Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands
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  • For correspondence: r.k.kortekaas@rug.nl
Janette K. Burgess
2Department of Medical Biology and Pathology, University of Groningen, Groningen, Netherlands
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Megan Webster
3Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany
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Reinoud Gosens
1Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands
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Abstract

IL11 was reported to induce the formation of myofibroblasts and their secretion of collagen, while its subcutaneous administration drives the development of pulmonary fibrosis in mice. Less is known as to how IL11 affects epithelial-mesenchymal communication associated with epithelial repair, and regarding which cell types are the main producers and responders to IL11 in vivo. Here we aim to investigate the role of IL11 in alveolar regeneration.

Epithelial progenitor cell behavior was studied using an organoid model, comprised of a co-culture of primary mouse CD31-CD45-Epcam+ cells with either CCL206 fibroblasts or primary human fibroblasts. After 14 days, the number and size of the organoids were determined, and immunofluorescent staining for Surfactant protein C (SPC) and acetylated tubulin (ACT) was performed to define alveolar vs airway organoids. Immunohistochemical staining of IL11 and IL11R was performed on human lung tissue to observe producer and responder cells of IL11 signaling.

The presence of rhIL11 significantly decreased the number of mouse/mouse and mouse/human organoids formed in a concentration-dependent manner, and the fraction of SPC+ organoids was reduced by rhIL11 whereas the fraction of SPC-ACT- organoids was increased. Organoid size was not affected. Immunohistochemistry revealed that IL11R is found in smooth muscle, airway epithelium and endothelium, whereas IL11 was observed in airway epithelium, alveolar type 2 cells and macrophages.

IL11 may impair epithelial progenitor function by suppressing their activation and by suppressing the formation of mature alveolar cell types. IL11R localization suggests mesenchymal activation by IL11 may contribute to the observed effects on progenitor function.

  • Idiopathic pulmonary fibrosis
  • Epithelial cell
  • Pharmacology

Footnotes

Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2050.

This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2021
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IL11 negatively impacts adult lung alveolar organoid formation
Rosa K. Kortekaas, Janette K. Burgess, Megan Webster, Reinoud Gosens
European Respiratory Journal Sep 2021, 58 (suppl 65) PA2050; DOI: 10.1183/13993003.congress-2021.PA2050

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IL11 negatively impacts adult lung alveolar organoid formation
Rosa K. Kortekaas, Janette K. Burgess, Megan Webster, Reinoud Gosens
European Respiratory Journal Sep 2021, 58 (suppl 65) PA2050; DOI: 10.1183/13993003.congress-2021.PA2050
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