Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

ABSTRACT: miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

PROVIDER: PRJNA511438 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

Project description:In type 1 diabetes (T1D), the appearance of multiple islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. However, the underlying molecular mechanisms in T cells that can promote aberrant activation thereby triggering autoimmune progression remain poorly understood. Here, we show that during early stages of islet autoimmunity a miRNA142-3p/Tet2 signaling axis in murine and human CD4+T cells interferes with the efficient induction of regulatory T (Treg) cells accompanied by impairments in Treg stability. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity, while its inhibition enhances Treg induction and stability accompanied by a reduction of islet autoimmunity in non-obese diabetic (NOD) mice. Mechanistically, using HITS-CLIP analyses we identify the methylcytosine dioxygenase Tet2 as a direct target of miR142-3p in CD4+T cells, thereby linking high miR142-3p levels to epigenetic remodeling and impairments in Treg induction and stability. These findings offer a new mechanistic model where during islet-autoimmunity miR142-3p/Tet2-mediated Treg instability can contribute to autoimmune activation and progression.

2019-11-14 | GSE124264 | GEO

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

2019-11-14 | GSE140064 | GEO

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

Project description:miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

| PRJNA588167 | ENA

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

Project description:miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

| PRJNA588161 | ENA

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes.

Project description:In type 1 diabetes, the appearance of islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in the destruction of pancreatic beta cells, molecular underpinnings promoting aberrant T cell activation remain poorly understood. Here, we show that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity and that its inhibition enhances Treg induction and stability, leading to reduced islet autoimmunity in non-obese diabetic mice. Using various cellular and molecular approaches we identify Tet2 as a direct target of miR142-3p, thereby linking high miR142-3p levels to epigenetic remodeling in Tregs. These findings offer a mechanistic model where during islet autoimmunity miR142-3p/Tet2-mediated Treg instability contributes to autoimmune activation and progression.

| S-EPMC6910913 | biostudies-literature

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

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

2019-11-14 | GSE140065 | GEO

miR-101a-3p impairs synaptic plasticity and contributes to synucleinopathy

Project description:miR-101a-3p impairs synaptic plasticity and contributes to synucleinopathy

| PRJNA803028 | ENA

CD74 deficiency impairs Treg accumulation and function in the tumor

Project description:CD74 deficiency impairs Treg accumulation and function in the tumor

| PRJNA954341 | ENA

Loss of TET2 Impairs Endothelial Angiogenesis via Downregulating STAT3 Target Genes

Project description:Loss of TET2 Impairs Endothelial Angiogenesis via Downregulating STAT3 Target Genes

| PRJNA822838 | ENA

14-3-3 protects AMPK phosphorylated TET2 from dephosphorylation by PP2A

Project description:Ten-eleven translocation-2 (TET2) is a member of the methylcytosine dioxygenase family of enzymes implicated in cancer and in aging due to its role as a global epigenetic modifier. TET2 has a large N-terminal domain followed by a catalytic C-terminal. Previous reports have demonstrated that the catalytic domain remains active independent of the N-terminal domain. As such, the function of the N-terminus of this large protein remains poorly characterized. Here, we identify that several isoforms of the 14-3-3 family of proteins bind TET2. 14-3-3s bind TET2 when phosphorylated at serine 99 (S99). AMPK-mediated phosphorylation at S99 promotes TET2 stability and increases global DNA 5-hydroxymethylcytosine. 14-3-3s’ interaction with TET2 serves to protect S99 phosphorylation. Disruption of this interaction leads to both reduced TET2 phosphorylation and decreased protein stability. Furthermore, we identify that the protein phosphatase 2A (PP2A) can interact with TET2 and dephosphorylates S99. Collectively, our study provides novel insights into the role of the N-terminal domain in TET2 regulation. Moreover, they demonstrate the dynamic nature of TET2 protein regulation that could have therapeutic implications for disease states resulting from reduced TET2 levels and/or activity.

2020-01-13 | PXD016160 | Pride

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