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  • Title: E-protein regulatory network links TCR signaling to effector Treg cell differentiation.
    Author: Han X, Huang H, Gao P, Zhang Q, Liu X, Jia B, Strober W, Hou B, Zhou X, Gao GF, Zhang F.
    Journal: Proc Natl Acad Sci U S A; 2019 Mar 05; 116(10):4471-4480. PubMed ID: 30770454.
    Abstract:
    T cell antigen receptor (TCR) signaling is essential for the differentiation and maintenance of effector regulatory T (Treg) cells. However, the contribution of individual TCR-dependent genes in Treg cells to the maintenance of immunotolerance remains largely unknown. Here we demonstrate that Treg cells lacking E protein undergo further differentiation into effector cells that exhibit high expression of effector Treg signature genes, including IRF4, ICOS, CD103, KLRG-1, and RORγt. E protein-deficient Treg cells displayed increased stability and enhanced suppressive capacity. Transcriptome and ChIP-seq analyses revealed that E protein directly regulates a large proportion of the genes that are specific to effector Treg cell activation, and importantly, most of the up-regulated genes in E protein-deficient Treg cells are also TCR dependent; this indicates that E proteins comprise a critical gene regulatory network that links TCR signaling to the control of effector Treg cell differentiation and function.
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