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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

ABSTRACT: To investigate the role of IkE5 in Treg cell biology, we established IkE5-deficient Treg cells from Foxp3-Cre IkE5 floxed mice. We then performed Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for several transcription factors and epigenetic regulators as well as the histone modification H3K27ac in wild-type and IkE5-deficient Treg cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE229590 | GEO | 2024/08/07

REPOSITORIES: GEO

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

Project description:To investigate the role of IkE5 in Treg cell biology, we established IkE5-deficient Treg cells from Foxp3-Cre IkE5 floxed mice. We then performed gene expression profiling analysis using data obtained from bulk RNA-seq of wild-type and IkE5-deficient Treg cells.

2024-08-07 | GSE229591 | GEO

Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

Project description:To investigate the role of IkE5 in Treg cell biology, we established IkE5-deficient Treg cells from Foxp3-Cre IkE5 floxed mice. We then performed assay for transposase-accessible chromatin (ATAC)-seq to evaluate the chromatin accessibility in wild-type and IkE5-deficient Treg cells.

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

Project description:Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

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Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

Project description:Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity

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FOXP3 exon 2 controls Treg stability and autoimmunity [RNA-seq]

Project description:Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing – a longer isoform (FOXP3 FL) containing all the coding exons and the other shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans yet their differences in controlling regulatory T cell phenotype and functionality remains unclear. Here we show that patients expressing only the shorter isoform failed to maintain self-tolerance and developed IPEX syndrome. Mice with Foxp3 exon 2 deletion developed excessive TFH and GC B cell responses and systemic autoimmune disease with anti-dsDNA and anti-nuclear autoantibody production and immune-complex glomerulonephritis. Regulatory T cells expressing FOXP3 ΔE2 were unstable and sufficient to induce autoimmunity when transferred into Tcrb-deficient mice. Mechanistically, FOXP3 ΔE2 isoform allows increased expression of selected cytokines but decreased expression of a set of Foxp3 positive regulators without altered binding to these gene loci. We demonstrate that exon 2 of FOXP3 is required to maintain Treg stability and immune homeostasis.

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