Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway
Author(s)
Ng, Benjamin
Cook, Stuart A
Schafer, Sebastian
Type
Journal Article
Abstract
Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
Date Issued
2020-12-01
Date Acceptance
2020-09-25
Citation
Experimental and Molecular Medicine, 2020, 52 (12), pp.1871-1878
ISSN
0378-8512
Publisher
Nature Publishing Group
Start Page
1871
End Page
1878
Journal / Book Title
Experimental and Molecular Medicine
Volume
52
Issue
12
Copyright Statement
© The Author(s) 2020
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction
in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if
changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If
material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction
in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if
changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If
material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000595038800002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Biochemistry & Molecular Biology
CNTF GENE
EPITHELIAL-CELLS
EXPRESSION
FIBROBLASTS
IDIOPATHIC PULMONARY-FIBROSIS
IL-11
IL-13-INDUCED INFLAMMATION
Life Sciences & Biomedicine
LUNG
Medicine, Research & Experimental
MUTATIONS
RECEPTOR
Research & Experimental Medicine
Science & Technology
Publication Status
Published
Date Publish Online
2020-12-01