IL-9 as a mediator of Th17-driven inflammatory disease
Open accessAbstract
We report that like other T cells cultured in the presence of transforming growth factor (TGF) β, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-β as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6–producing macrophages in the central nervous system, as well as mast cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9 as a Th17-derived cytokine that can contribute to inflammatory disease.
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Culture with TGF-β1 may increase IL-9 production from multiple cell types.
“culture with TGF-β1 may increase IL-9 production from multiple cell types26.”
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 [26]
The Results and Discussion section (‘Th17 cells produce IL-9’; page not provided) reports dose-dependent induction of IL-9 by TGF-β and IL-9 production under TGF-β culture conditions in several T-cell subsets. It does not specify the β1 isoform or establish the effect in cell types beyond T cells. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIL-9 has been shown to promote the development of TH17 cells and increase Treg activity.
“Most recently, IL-9 has been shown to promote the development of TH17 cells, while increasing Treg activity25,26”
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 [26]
The Abstract reports that blocking IL-9 or its receptor correlates with fewer Th17 cells in the CNS, supporting a role for IL-9 in Th17-driven disease. But Results and Discussion says initial Th17 priming appeared equivalent to controls, so the paper does not establish that IL-9 promotes Th17 development. It reports that Treg cells produce IL-9 and links IL-9 to immunosuppression, but does not show increased Treg activity. (LLM, conf=0.84)
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- Authors
- Nowak, E. C., Weaver, C. T., Turner, H., Begum-Haque, S., Becher, B., Schreiner, B., Coyle, A. J., Kasper, L. H., & Noelle, R. J.
- Affiliations
- Dartmouth College (US)
- University of Alabama at Birmingham (US)
- Dartmouth Cancer Center (US)
- University Hospital Zurich (CH)
- Department of Autoimmunity and Inflammation, MedImmune, Gaithersburg, MD 20878 4
- Corresponding author
- Noelle, Randolph J.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-07-13
- Volume
- 206
- Issue
- 8
- Pages
- 1653-1660
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2722185
- OpenAlex
- W2100645101
- Cited by
- 393
- References
- 6
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 18 · 2023: 21 · 2022: 16 · 2021: 14 · 2020: 28 · 2019: 16 · 2018: 22 · 2017: 23 · 2016: 33 · 2015: 31 · 2014: 19 · 2013: 26 · 2012: 41
- FWCI
- 15.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI048667, T32AI07363, AI048667, T32AI007363)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- IL-9, Th17 cells, experimental autoimmune encephalomyelitis, multiple sclerosis, TGF-beta, interleukin-6, IL-9 receptor, mast cells, macrophages, neuroinflammation, cytokine neutralization
- MeSH terms
- Animals, Encephalomyelitis, Autoimmune, Experimental, Female, T-Lymphocytes, Helper-Inducer, Mice, Inbred C57BL, Spinal Cord, T-Lymphocyte Subsets, Interleukin-9, Mice, Knockout, Inflammation Mediators, Adoptive Transfer, Mice, Receptors, Interleukin-9, In Vitro Techniques
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