TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (WGBS)

TET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further oxidation products in DNA. Here we report that simultaneous deletion of Tet2 and Tet3 in mouse double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T (iNKT) cells. Tet2-Tet3-double-deficient (DKO) iNKT cells displayed pronounced skewing towards the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in uncontrolled expansion dependent on the nonclassical MHC protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring proper development and maturation and suppressing aberrant T cell antigen receptor (TCR)-mediated proliferation.

Dataset features

Information

Specifications

Application:	BS-seq analysis
Number of samples:	4
Release date:	Nov 21 2016
Last update date:	Oct 24 2018
Access:	Public
Chemicals:	5-Methylcytosine
Dataset link	TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (WGBS)

Experimental Protocol

In order to address the impact of the loss of Tet2/3 proteins in DNA methylation in iNKT cells we compared by WGBS seq the methylome of wild INKT cells, Tet2/3 DKO iNKT cells and expanded Tet2/3 DKO iNKT cells in congenic recipients.

Repositories

GEO

GSE72116

ENA

SRP062482

BioProject

PRJNA293086

Dataset features

Specifications

Experimental Protocol

Repositories

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