STAT6-dependent regulation of Th9 development
Open accessAbstract
Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration of signals that may promote the development of opposing pathways. A recent example of this paradigm is the IL-9–secreting Th9 cell that develops in response to TGF-β and IL-4, cytokines that, in isolation, promote the development of inducible regulatory T cells and Th2 cells, respectively. To determine how the balance of these factors results in priming for IL-9 secretion, we examined the effects of each pathway on transcription factors that regulate Th cell differentiation. We demonstrated that TGF-β induces the PU.1-encoding Sfpi1 locus and that this is independent of IL-4–induced STAT6 activation. IL-4–activated STAT6 is required for repressing the expression of T-bet and Foxp3 in Th9 cells, transcription factors that inhibit IL-9 production, and STAT6 is required for the induction of IRF4, which promotes Th9 development. These data established a transcription factor network that regulates IL-9 and demonstrated how combinations of cytokine signals generate cytokine-secreting potential by altering the expression of a panel of transcription factors.
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PU.1, rather than IRF4, GATA3, or STAT6, is the main driver for Th9 cell differentiation.
“Moreover, the transcription factor PU.1, rather than IRF4, GATA3, or STAT6, is the main driver for Th9 cell differentiation.20, 21”
From PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells (2022) · cites this paper as [21]
The Introduction identifies both PU.1 and IRF4 as required for Th9 development. The Results say STAT6 is required for Th9 development, and the Discussion describes a network of factors rather than PU.1 as the main driver instead of the others. Our copy does not provide page numbers for these passages. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredIn Th9 cells, IL-9 gene expression is regulated by TGFβ, IL-4, and IL-33 and transcription factors like PU.1, STAT6, GATA3, and IRF4.
“In these cells, IL-9 gene expression is regulated by the cytokines TGFβ, IL-4, and IL-33 and transcription factors like PU.1, STAT6, GATA3, and IRF4.19–22”
From PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells (2022) · cites this paper as [21]
The Introduction and Discussion describe TGFβ and IL-4 signals and roles for PU.1, STAT6, GATA3, and IRF4 in Th9-cell IL-9 regulation. The Results also show that excess GATA3 decreases IL-9 production, so its role is not simply promotional. No passage in our copy supports the attributed role for IL-33 (searched: IL-33). (LLM, conf=0.88)
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STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus
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- Authors
- Goswami, R., Jabeen, R., Yagi, R., Pham, D., Zhu, J., Goenka, S., & Kaplan, M. H.
- Affiliations
- Indiana University Indianapolis (US)
- National Institutes of Health (US)
- Corresponding author
- Goswami, Ritobrata
- Jabeen, Rukhsana
- Pham, Duy
- Goenka, Shreevrat
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-02-01
- Volume
- 188
- Issue
- 3
- Pages
- 968-975
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3262957
- OpenAlex
- W1925756130
- Cited by
- 240
- References
- 39
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 16 · 2022: 10 · 2021: 17 · 2020: 16 · 2019: 21 · 2018: 16 · 2017: 21 · 2016: 21 · 2015: 24 · 2014: 15 · 2013: 25 · 2012: 15
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL093105, HL093105)
- National Institute of Allergy and Infectious Diseases (AI057459, R01AI057459, ZIAAI001169)
- 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
- Th9 cells, STAT6, IL-9, TGF-beta, IL-4, T helper cell differentiation, transcription factors, PU.1, T-bet, Foxp3, IRF4, regulatory T cells, Th2 cells, cytokine signaling
- MeSH terms
- Interferon Regulatory Factor-4, Proto-Oncogene Protein Spi-1, Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Proto-Oncogene Proteins, Signal Transduction, Transcriptional Activation, Trans-Activators, Interleukin-4, Cytokines, Interleukin-9, STAT6 Transcription Factor, Interferon Regulatory Factors, Mice, Gene Regulatory Networks
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