Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE189077 | GEO | 2022/02/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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: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 [RNA-seq]

2022-02-28 | GSE189075 | GEO

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

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

| PRJNA781244 | ENA

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 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.

| S-EPMC10575732 | biostudies-literature

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

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance.

Project description:Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor (IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to the pleiotropic effects of IL-2R signaling, it is unclear how STAT5 acts directly on the Foxp3 locus to promote its expression. Here, we report that IL-2 - STAT5 signaling converged on an enhancer (CNS0) during Foxp3 induction. CNS0 facilitated the IL-2 dependent CD25+Foxp3- precursor to Treg cell transition in the thymus. Its deficiency resulted in impaired Treg cell generation in neonates, which was partially mitigated with age. While the thymic Treg cell paucity caused by CNS0 deficiency did not result in autoimmunity on its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS0 enhancer activity ensures robust Treg cell differentiation early in postnatal life and cooperatively with other tolerance mechanisms minimizes autoimmunity.

| S-EPMC8317508 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data