Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

ABSTRACT: T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment¹. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction². However, the molecular mechanisms that underlie this dysfunction remain unclear. Here, using an in vitro T cell tolerance induction system in mice, we characterize genome-wide epigenetic and gene expression features in tolerant T cells, and show that they are distinct from effector and regulatory T cells. Notably, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deleti

SUBMITTER: Liu X 

PROVIDER: S-EPMC6507425 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature