IL-9 induces differentiation of T H 17 cells and enhances function of FoxP3 + natural regulatory T cells
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The development of T helper (T H )17 and regulatory T (T reg ) cells is reciprocally regulated by cytokines. Transforming growth factor (TGF)-β alone induces FoxP3 + T reg cells, but together with IL-6 or IL-21 induces T H 17 cells. Here we demonstrate that IL-9 is a key molecule that affects differentiation of T H 17 cells and T reg function. IL-9 predominantly produced by T H 17 cells, synergizes with TGF-β1 to differentiate naïve CD4 + T cells into T H 17 cells, while IL-9 secretion by T H 17 cells is regulated by IL-23. Interestingly, IL-9 enhances the suppressive functions of FoxP3 + CD4 + T reg cells in vitro, and absence of IL-9 signaling weakens the suppressive activity of nT regs in vivo, leading to an increase in effector cells and worsening of experimental autoimmune encephalomyelitis. The mechanism of IL-9 effects on T H 17 and T regs is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses.
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IL-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 [25]
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Control of Regulatory T Cell Development by the Transcription Factor <i>Foxp3</i>
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IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
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- Authors
- Elyaman, W., Bradshaw, E. M., Uyttenhove, C., Dardalhon, V., Awasthi, A., Imitola, J., Bettelli, E., Oukka, M., van Snick, J., Renauld, J.-C., Kuchroo, V. K., & Khoury, S. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Ludwig Cancer Research (BE)
- Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université Catholique de Louvain, Brussels, Belgium
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-08-04
- Volume
- 106
- Issue
- 31
- Pages
- 12885-12890
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2722314
- OpenAlex
- W2105132195
- Cited by
- 498
- References
- 6
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 34 · 2023: 33 · 2022: 27 · 2021: 28 · 2020: 31 · 2019: 28 · 2018: 31 · 2017: 36 · 2016: 38 · 2015: 25 · 2014: 26 · 2013: 27 · 2012: 36
- FWCI
- 14.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R56AI058680, R01AI073542, R01AI058680, R01AI067472, AI 058680, R01AI043496, AI 043496)
- National Institute of Neurological Disorders and Stroke (R01NS059996)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-9, Th17 cells, regulatory T cells, Foxp3, TGF-β1, IL-23, STAT3 signaling, STAT5 signaling, CD4+ T cell differentiation, suppressive function, experimental autoimmune encephalomyelitis, interleukin-6, IL-21
- MeSH terms
- Amino Acid Sequence, Animals, Cell Differentiation, Female, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Interleukin-9, Interleukin-17, T-Lymphocytes, Regulatory, STAT3 Transcription Factor, STAT5 Transcription Factor, Mice, Forkhead Transcription Factors, Interleukin-23, Transforming Growth Factor beta1
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