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Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

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Tang, W, Geba, G P, Zheng, T, Ray, P, Homer, R J, Kuhn, C, Flavell, R A, Elias, J A·1996·Journal of Clinical Investigation

DOI 10.1172/jci119113PMC PMC507752

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Abstract

Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.

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Authors: Tang, W., Geba, G. P., Zheng, T., Ray, P., Homer, R. J., Kuhn, C., Flavell, R. A., & Elias, J. A.
Affiliations: Yale University (US)
United States Department of Veterans Affairs (US)
Miriam Hospital (US)
Brown University (US)
ORCID: Tang, W
Geba, G P
Ray, P
Homer, R J
Kuhn, C
Flavell, R A
Elias, J A
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1996-12-15
Volume: 98
Issue: 12
Pages: 2845-2853
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119113
PMC: PMC507752
OpenAlex: W2075223992
Cited by: 210
References: 59
Citations by year: 2026: 2 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 9 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 5
FWCI: 6.07
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01hl054989-03, 5r01hl036708-12)
National Heart, Lung, and Blood Institute (HL54989, HL-36708)
National Institute of Allergy and Infectious Diseases (AI-34593)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: interleukin-11, airway inflammation, airway remodeling, airway obstruction, airway hyperresponsiveness, transgenic mice, lymphocytic inflammation, B cells, T cells, subepithelial fibrosis, collagen deposition, myofibroblasts, smooth muscle cells, fibroblasts, airway resistance, methacholine
MeSH terms: Airway Obstruction, Airway Resistance, Animals, Cloning, Molecular, Disease Models, Animal, Gene Expression Regulation, Histocytochemistry, Immunohistochemistry, Lung, Mice, Transgenic, Microscopy, Electron, Promoter Regions, Genetic, Proteins, Pulmonary Fibrosis, Uteroglobin, Blotting, Southern, Blotting, Northern, Methacholine Chloride, Interleukin-11, Mice

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Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

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