Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA137547 | ENA |
REPOSITORIES: ENA
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Project description:The forkhead transcription factor, Foxp3, is pivotal to the development and function of CD4+CD25+ T regulatory (Treg) cells that limit autoimmunity and maintain immune homeostasis. Previous data indicated that many of the functions of Foxp3 are controlled by the acetylation of several lysines within the forkhead domain. We now show that mutation of each of two lysines within the forkhead domain of Foxp3, lysine at position 382 (K17) and lysine at position 393 (K18), impaired Treg suppressive function in vivo and in vitro. Lysine mutations also decreased Treg expression of multiple functionally important Foxp3-regulated genes, and inhibited the promoter remodeling of target genes (CTLA-4 and IL-2) without affecting Foxp3 expression level. These data point to the need for a further understanding of the effects of various post-translational modifications on Foxp3 function. Our studies also provide a rationale for developing small molecule inhibitors of such post-translational modifications so as to regulate Foxp3+ Treg function clinically. RNA from three independent samples from magnetically separated CD4+CD25- T-effector cells transduced with EV, WT-Fopx3, Foxp3-K17R or Foxp3-K18R
2011-02-05 | E-GEOD-27082 | biostudies-arrayexpress
Project description:The forkhead transcription factor, Foxp3, is pivotal to the development and function of CD4+CD25+ T regulatory (Treg) cells that limit autoimmunity and maintain immune homeostasis. Previous data indicated that many of the functions of Foxp3 are controlled by the acetylation of several lysines within the forkhead domain. We now show that mutation of each of two lysines within the forkhead domain of Foxp3, lysine at position 382 (K17) and lysine at position 393 (K18), impaired Treg suppressive function in vivo and in vitro. Lysine mutations also decreased Treg expression of multiple functionally important Foxp3-regulated genes, and inhibited the promoter remodeling of target genes (CTLA-4 and IL-2) without affecting Foxp3 expression level. These data point to the need for a further understanding of the effects of various post-translational modifications on Foxp3 function. Our studies also provide a rationale for developing small molecule inhibitors of such post-translational modifications so as to regulate Foxp3+ Treg function clinically.
2011-02-05 | GSE27082 | GEO
Project description:Mbd2 promotes Foxp3 demethylation and T-regulatory cell function
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Project description:The forkhead transcription factor Foxp3 is essential for the development of CD4+CD25+ regulatory T (Treg) cells and prevention of autoimmunity, but how it controls the Treg gene expression program is not understood. We describe here genome-wide location and expression data that identify Foxp3 target genes and report that many Foxp3 target genes are key modulators of T cell activation and function. Remarkably, the predominant effect of Foxp3 binding is to suppress the activation of target genes upon T cell stimulation. Foxp3 suppression of its targets appears to be crucial for the normal function of Treg cells because overactive variants of some target genes are known to be associated with autoimmune disease.
2007-01-27 | E-TABM-154 | biostudies-arrayexpress
Project description:The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4+CD25+ regulatory T cells (TREG), which play a key role in maintaining self tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by the Nuclear Factor of Activated T cells (NFAT). Various mechanisms have been proposed by which FOXP3 mediates these effects. Using novel HEK cell lines that inducibly express either wild-type (WT) or mutant FOXP3, we have identified genome-wide expression patterns showing among other features that NFAT2 as an early target of FOXP3-mediated transcriptional repression. Six biological replicates of wild-type induced FOXP3 cell lines and six biological replicates of mutated FOXP3 cell line were studied.
2010-05-15 | E-GEOD-13798 | biostudies-arrayexpress
Project description:Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-regulatory Cell Development and Function
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Project description:FOXP3+ regulatory T cell development and function require histone/protein deacetylase 3
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Project description:The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4+CD25+ regulatory T cells (TREG), which play a key role in maintaining self tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by the Nuclear Factor of Activated T cells (NFAT). Various mechanisms have been proposed by which FOXP3 mediates these effects. Using novel HEK cell lines that inducibly express either wild-type (WT) or mutant FOXP3, we have identified genome-wide expression patterns showing among other features that NFAT2 as an early target of FOXP3-mediated transcriptional repression.
2008-12-04 | GSE13798 | GEO
Project description:Inhibition of p300 impairs Foxp3+ T-regulatory cell function and promotes anti-tumor immunity
| PRJNA208587 | ENA