Stable inhibitory activity of regulatory T cells requires the transcription factor Helios

Science. 2015 Oct 16;350(6258):334-9. doi: 10.1126/science.aad0616.

Abstract

The maintenance of immune homeostasis requires regulatory T cells (T(regs)). Given their intrinsic self-reactivity, T(regs) must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3(+) CD4 and Qa-1-restricted CD8 T(regs) results in defective regulatory activity and autoimmunity in mice. Helios-deficient T(regs) develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 T(regs) also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. The definition of Helios as a key transcription factor that stabilizes T(regs) in the face of inflammatory responses provides a genetic explanation for a core property of T(regs).

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / genetics
  • Autoimmunity / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Kidney / immunology
  • Liver / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pancreas / immunology
  • STAT5 Transcription Factor / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • STAT5 Transcription Factor
  • Transcription Factors
  • Zfpn1a2 protein, mouse

Associated data

  • GEO/GSE72997
  • GEO/GSE73015