Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology
Abstract
IL-9 is a pleiotropic cytokine with multiple functions on many cell types involved in the pathology of human asthma. The constitutive overexpression of IL-9 in the lungs of transgenic mice resulted in an asthma-like phenotype. To define the contribution of IL-9 to lung inflammation we generated transgenic mice in which lung-specific expression of the IL-9 transgene is inducible by doxycycline. Transgene induction resulted in lymphocytic and eosinophilic infiltration of the lung, airway epithelial cell hypertrophy with mucus production, and mast cell hyperplasia, similar to that seen in mice that constitutively expressed IL-9 in their lungs. Various cytokines, including IL-4, IL-5, and IL-13, were expressed in the lung in response to IL-9. Blockade of IL-4 or IL-5 following IL-9 induction reduced airway eosinophilia without affecting mucus production. In contrast, neutralization of IL-13 completely abolished both lung inflammation and mucus production. These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully.
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Transgenic expression of Il9 results in allergic inflammation.
“Transgenic expression of Il9 results in allergic inflammation11–13.”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [13]
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Self-citationIL-9 and its receptor in allergic and nonallergic lung disease: Increased expression in asthma
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New insights into the pathogenesis of asthma
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- Authors
- Temann, U.-A., Ray, P., & Flavell, R. A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Flavell, Richard A.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-01-01
- Volume
- 109
- Issue
- 1
- Pages
- 29-39
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4230086548
- Cited by
- 201
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 12 · 2016: 12 · 2015: 9 · 2014: 6 · 2013: 10 · 2012: 10
- FWCI
- 11.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (HL-56389)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- IL-9, asthma, Th2 cytokines, IL-4, IL-5, IL-13, lung inflammation, eosinophil infiltration, mucus production, mast cell hyperplasia, doxycycline-inducible expression, cytokine inhibition
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