STAT6 controls the stability and suppressive function of regulatory T cells
Abstract: Signal transducer and activator of transcription 6 (STAT6) promotes tumorigenesis by decreasing the Forkhead box P3+ (Foxp3+) cell frequency allowing for the infiltration of inflammatory cells during the early stages of colitis‐associated cancer (CAC). In this study, we dissected the role of STAT6 in the generation of inducible in vitro regulatory T cells (iTregs) and peripheral in vivo Tregs (pTregs) under inflammatory conditions. In in vitro assays, when STAT6 was lacking, iTregs preserved a stable phenotype and expressed high levels of Foxp3 and CD25 during long expansion periods, even in the presence of IL‐6. This effect was associated with increased in vitro suppressive ability, over‐expression of programmed death‐1 (PD‐1), CTLA‐4, and Foxp3, and decreased IFN‐γ expression. Furthermore, iTregs developed during STAT6 deficiency showed a higher demethylation status for the FOXP3 Treg‐specific demethylated region (TSDR), coupled with lower DNA methyltransferase 1 (DNMT1) mRNA expression, suggesting that STAT6 may lead to Foxp3 silencing. Using a mouse model of CAC, the STAT6‐/‐ pTregs expressed a more activated phenotype at the intestine, had higher suppressive capacity, and expressed more significant levels of PD‐1 and latency‐associated peptide of TGF‐β (LAP) associated with their ability to attenuate tumor development. These data suggest that STAT6 signaling impairs the induction, stability, and suppressive capacity of Tregs developed in vitro or in vivo during gut inflammation.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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STAT6 controls the stability and suppressive function of regulatory T cells ; day:03 ; month:03 ; year:2023 ; extent:17
European journal of immunology ; (03.03.2023) (gesamt 17)
- Creator
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Arroyo‐Olarte, Rubén D.
Rivera‐Rugeles, Ana
Nava‐Lira, Eduardo
Sánchez‐Barrera, Ángel
Ledesma‐Soto, Yadira
Saavedra, Rafael
Armas‐López, Leonel
Terrazas, Luis I.
Ávila‐Moreno, Federico
Leon‐Cabrera, Sonia
- DOI
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10.1002/eji.202250128
- URN
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urn:nbn:de:101:1-2023030314394470483722
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:55 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Arroyo‐Olarte, Rubén D.
- Rivera‐Rugeles, Ana
- Nava‐Lira, Eduardo
- Sánchez‐Barrera, Ángel
- Ledesma‐Soto, Yadira
- Saavedra, Rafael
- Armas‐López, Leonel
- Terrazas, Luis I.
- Ávila‐Moreno, Federico
- Leon‐Cabrera, Sonia
Other Objects (12)
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Unexpected Phenotype of STAT6 Heterozygous Mice Implies Distinct STAT6 Dosage Requirements for Different IL-4 Functions
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Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells
The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation
STAT6 regulated B cell responses
JunB regulates homeostasis and suppressive functions of effector regulatory T cells
PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability
Stat6-vermittelte Genregulation in eukaryontischen Zellen
Stat6-vermittelte-Genregulation in eukaryontischen Zellen
A sphingolipid rheostat controls apoptosis versus apical cell extrusion as alternative tumour-suppressive mechanisms
Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function
Canonical androgen response element motifs are tumor suppressive regulatory elements in the prostate
Unexpected Phenotype of STAT6 Heterozygous Mice Implies Distinct STAT6 Dosage Requirements for Different IL-4 Functions
WASH activation controls endosomal recycling and EGFR and Hippo signaling during tumor-suppressive cell competition
Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells
The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation
STAT6 regulated B cell responses
JunB regulates homeostasis and suppressive functions of effector regulatory T cells
PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability
Stat6-vermittelte Genregulation in eukaryontischen Zellen
Stat6-vermittelte-Genregulation in eukaryontischen Zellen
A sphingolipid rheostat controls apoptosis versus apical cell extrusion as alternative tumour-suppressive mechanisms
Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function
Canonical androgen response element motifs are tumor suppressive regulatory elements in the prostate
Unexpected Phenotype of STAT6 Heterozygous Mice Implies Distinct STAT6 Dosage Requirements for Different IL-4 Functions