Genomics

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Global chromatin accessibility of gene locus in CD4+ T cells activated with or without OX40 costimulation


ABSTRACT: OX40 is a T cell costimulatory molecule in the tumor necrosis factor receptor (TNFR) superfamily. Unlike other costimulatory molecules, OX40 is not expressed by naive T cells, but its expression is rapidly induced following T cell activation, and OX40 costimulation plays a critical role in cell survival, proliferation, and generation of memory cells. We used ATAC-seq to detail the chromatin accessibility of gene locus of activated CD4 T cells with or without OX40 costimulation in the presence of TGF-β1 and IL-2 and identified distinct classes of genes after OX40 costimulation. Overall design: Naive CD4+ T cells (CD62LhighCD44lowFoxp3−) were sorted from C57/Bl6 Foxp3-eGFP reporter mice, and activated in vitro with soluble anti-CD3 mAb and mitomycin C-treated Wt APCs or OX40L-Tg APCs in the presence of TGF-β1 and IL-2 in 96-well round bottom tissue-culture plates. Forty-eight hours later, living CD4+ T cells were sorted from cultures by flow cytometry. ATAC-seq was performed at Active Motif (Carlsbad, CA).

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Xiaolong Zhang  

PROVIDER: GSE114568 | GEO | 2018-05-18

REPOSITORIES: GEO

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Publications

OX40 Costimulation Inhibits Foxp3 Expression and Treg Induction via BATF3-Dependent and Independent Mechanisms.

Zhang Xiaolong X   Xiao Xiang X   Lan Peixiang P   Li Junhui J   Dou Yaling Y   Chen Wenhao W   Ishii Naoto N   Chen Shuqiu S   Xia Bo B   Chen Kaifu K   Taparowsky Elizabeth E   Li Xian C XC  

Cell reports 20180701 3


Naive CD4<sup>+</sup> T cells can be converted to Foxp3<sup>+</sup> T regulatory cells (Tregs) in the periphery (iTregs), where induction of Foxp3 gene expression is central to Treg differentiation. OX40 signaling is known to inhibit Foxp3 expression and Treg induction, but the underlying mechanisms remain poorly defined. Here, we found that OX40 costimulation activates two distinct molecular pathways to suppress Foxp3 expression in freshly activated naive CD4<sup>+</sup> T cells. Specifically,  ...[more]

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