Ets Transcription Factor GABP Controls T Cell Homeostasis and Immunity

Nat Commun. 2017 Oct 20;8(1):1062. doi: 10.1038/s41467-017-01020-6.

Abstract

Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigens / immunology
  • Binding Sites
  • CD4 Antigens / genetics
  • Cell Proliferation
  • Cells, Cultured
  • DNA Replication
  • GA-Binding Protein Transcription Factor / genetics
  • GA-Binding Protein Transcription Factor / physiology*
  • Homeostasis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Minichromosome Maintenance Proteins / metabolism
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • Transcription, Genetic

Substances

  • Antigens
  • CD4 Antigens
  • GA-Binding Protein Transcription Factor
  • Gabpa protein, mouse
  • Minichromosome Maintenance Proteins