CD4 + Regulatory T Cells Control T H 17 Responses in a Stat3-Dependent Manner
Open accessAbstract
Outfoxing Immune Excess: Immune responses are kept in check by Foxp3-expressing CD4 + -regulatory T cells (T regs ) through a variety of mechanisms. Expression of specific transcription factors directs T reg responses into distinct T helper cell lineages; however, the transcription factors that regulate particular helper lineages have not been completely characterized. Chaudhry et al. (p. 986 , published online 1 October) show that the transcription factor Stat3, that is required for the initial differentiation of T H 17-effector T cells, is also required for T reg cell-mediated suppression of T H 17-mediated immune responses. Mice carrying a T reg cellspecific deletion in Stat3 succumb to an intestinal inflammatory disease driven by uncontrolled T H 17 responses. Thus, different classes of immune responses can result from the expression of helper lineage–specific transcription factors.
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STAT3 and Foxp3 coregulate IL-10 in Tregs through histone acetyl transferase-1/FoxP3-mediated epigenetic modification of the IL-10 promoter, maintaining the ability of Foxp3+ Tregs to inhibit inflammatory Th17 cells.
“STAT3 and Foxp3 appear to coregulate IL10 in T-regs”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Chaudhry et al., 2009
The supplied passage labeled Abstract reports that Foxp3 associates with active Stat3 in Tregs and that Il10 is among the genes dependent on both, supporting the hedged coregulation statement in the verbatim citing sentence. The copy does not establish histone acetyltransferase-1–mediated modification of the Il10 promoter or show that this particular mechanism maintains Th17 suppression; its promoter-binding experiments concern Il6 and Tgfb1 instead. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAn increasing list of transcription factors, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1, regulate both effector T cell function and regulatory T cell function.
“an increasing list of transcription factors now shown to regulate both effector T cell function and regulatory T cell function, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1 [98–105].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [99]
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“…coregulate IL10 in T-regs (Chaudhry et al., 2011) through histone acetyl transferase-1/FoxP3-mediated epigenetic modification of the IL-10 promoter (Chaudhry et al., 2009, 2011; Chaudhry and Rudensky, 2013), thus maintaining the ability of Foxp31 Tregs to inhibit inflammatory Th17 cells (Chaudhry…”
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- Authors
- Chaudhry, A., Rudra, D., Treuting, P., Samstein, R. M., Liang, Y., Kas, A., & Rudensky, A. Y.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Washington (US)
- Corresponding author
- Rudensky, Alexander Y.
- ORCID
- Venue
- Science
- Published
- 2009-11-13
- Volume
- 326
- Issue
- 5955
- Pages
- 986-991
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4408196
- OpenAlex
- W2029640857
- Cited by
- 1,000
- References
- 28
- Citations by year
- 2026: 23 · 2025: 33 · 2024: 40 · 2023: 35 · 2022: 43 · 2021: 52 · 2020: 57 · 2019: 70 · 2018: 67 · 2017: 58 · 2016: 59 · 2015: 85 · 2014: 70 · 2013: 76 · 2012: 79
- FWCI
- 33.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (T32GM007739)
- National Institute of Allergy and Infectious Diseases (AI034206, R01AI061816, AI061816, R37AI034206, R01AI034206)
- 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
- CD4+ regulatory T cells, Th17 cells, STAT3, T cell suppression, intestinal inflammation, autoimmune disease, immune tolerance, STAT transcription factors, T cell differentiation
- MeSH terms
- Animals, Female, T-Lymphocytes, Helper-Inducer, Interferon-gamma, Intestine, Large, Lymph Nodes, Lymphocyte Activation, Male, Mice, Inbred C57BL, Phosphorylation, Spleen, Inflammatory Bowel Diseases, T-Lymphocyte Subsets, Cytokines, Cell Lineage, Interleukin-17, T-Lymphocytes, Regulatory, STAT3 Transcription Factor, Mice, Forkhead Transcription Factors, Receptors, CCR6
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