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Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance

ABSTRACT: Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance

PROVIDER: PRJNA781244 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16967457_1.fastq.gz	Fastqsanger.gz
	SRR16967457_2.fastq.gz	Fastqsanger.gz
	SRR16967458_1.fastq.gz	Fastqsanger.gz
	SRR16967458_2.fastq.gz	Fastqsanger.gz
	SRR16967459_1.fastq.gz	Fastqsanger.gz

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Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance.

Project description:Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance.

| PRJNA781461 | ENA

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [ChIP-seq]

Project description:Regulatory T (Treg) cells are crucial for maintaining peripheral immune tolerance and preventing destructive autoreactive responses, but how heterogeneous Treg populations establish tolerant status remains unclear. Here, we found that Zinc finger protein 335 (Zfp335) is indispensable for the differentiation and maintenance of effector Treg (eTreg) population and immunological self-tolerance in neonates. Mice with Zfp335 deletion in Treg cells exhibit early-onset autoimmune disease with severe inflammation in multiple organs and unrestricted activation and expansion of conventional T cells. Zfp335-deficient Treg cells display dysfunctional and pathogenic features together with multiple defects in proliferation, survival and suppressive function. Importantly, our single-cell RNA sequencing (scRNA-seq) analyses reveal distinct Treg populations and that Zfp335 deficiency causes an almost complete loss of eTreg population along with significant accumulation of dysfunctional Treg populations. Mechanistically, Zfp335 controls both fate decision and homeostasis of eTreg cells by directly targeting genes associated with homeostasis and oxidation-fueled oxidative phosphorylation (OXPHOS) and PI3K-Akt-mTOR metabolic pathways. Our data establish the concept that Zfp335 serves as a checkpoint and safeguard for eTreg lineage commitment and maintenance.

2022-02-28 | GSE189076 | GEO

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [ChIP-seq]

Project description:Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [ChIP-seq]

| PRJNA781470 | ENA

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [RNA-seq]

Project description:Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [RNA-seq]

| PRJNA781471 | ENA

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance

2022-05-01 | GSE189041 | GEO

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [RNA-seq]

2022-02-28 | GSE189075 | GEO

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance.

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

2022-02-28 | GSE189077 | GEO

BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells

Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which self renew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineage commitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis. This SuperSeries is composed of the SubSeries listed below.

2020-05-12 | GSE128176 | GEO

Genome-wide profiling of Zfp335 binding sites in thymocytes

Project description:The generation of naM-CM-/ve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naM-CM-/ve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. 4 Zfp335 ChIP-seq samples and 2 input samples with WT vs. blt/blt thymocytes.

2014-10-17 | E-GEOD-58333 | biostudies-arrayexpress

Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation

Project description:Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation

| PRJNA781268 | ENA