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

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

PROVIDER: PRJNA781268 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16969965_1.fastq.gz	Fastqsanger.gz
	SRR16969965_2.fastq.gz	Fastqsanger.gz
	SRR16969966_1.fastq.gz	Fastqsanger.gz
	SRR16969966_2.fastq.gz	Fastqsanger.gz

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

Project description:Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

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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.

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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

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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 [ChIP-seq]

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

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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]

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

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

Project description:We utilized single-cell RNA sequencing (scRNA-seq) to carry out comparative transcriptome analysis in Tregs from the spleens of WT and KO (Zfp335fl/flFoxp3-Cre).

2023-10-10 | GSE189058 | 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