E-protein regulatory network links TCR signaling to effector Treg cell differentiation.
Proc Natl Acad Sci U S A
; 116(10): 4471-4480, 2019 03 05.
Article
in En
| MEDLINE
| ID: mdl-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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Receptors, Antigen, T-Cell
/
Signal Transduction
/
Cell Differentiation
/
T-Lymphocytes, Regulatory
/
Basic Helix-Loop-Helix Transcription Factors
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2019
Type:
Article
Affiliation country:
China