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Canonical Wnt signaling negatively modulates T regulatory cell function

ABSTRACT: Foxp3 is crucial for both the development and function of regulatory T cells (Treg),however the post-translational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that TCF1 and Foxp3 interact in the nucleus of Treg, and that active Wnt-signaling disrupts Foxp3 transcriptional activity. Utilizing a global ChIP-seq comparison we demonstrate considerable overlap between Foxp3 and Wnt target genes in Treg. Activation of Wnt signaling significantly reduces Treg-mediated suppression both in vitro and in vivo, while disruption of Wnt signaling in Treg enhances their suppressive capacity. Activation of effector T cells increases Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced by activated mononuclear cells under inflammatory conditions represses Treg function allowing a productive immune response, but if uncontrolled could lead to the development of autoimmunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE49199 | GEO | 2013/07/26

SECONDARY ACCESSION(S): PRJNA213297

REPOSITORIES: GEO

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Canonical Wnt signaling negatively modulates T regulatory cell function

Project description:Foxp3 is crucial for both the development and function of regulatory T cells (Treg),however the post-translational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that TCF1 and Foxp3 interact in the nucleus of Treg, and that active Wnt-signaling disrupts Foxp3 transcriptional activity. Utilizing a global ChIP-seq comparison we demonstrate considerable overlap between Foxp3 and Wnt target genes in Treg. Activation of Wnt signaling significantly reduces Treg-mediated suppression both in vitro and in vivo, while disruption of Wnt signaling in Treg enhances their suppressive capacity. Activation of effector T cells increases Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced by activated mononuclear cells under inflammatory conditions represses Treg function allowing a productive immune response, but if uncontrolled could lead to the development of autoimmunity. Beta catenin ChIP-seq in Treg

2013-07-26 | E-GEOD-49199 | biostudies-arrayexpress

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Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface

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Quantitative Proteomics Reveals Specialized Wiring of Signaling Pathways that Protects Human Regulatory T Cell Identity - 2 populations in vitro

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Quantitative Proteomics Reveals Specialized Wiring of Signaling Pathways that Protects Human Regulatory T Cell Identity - 5 populations ex vivo

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