The NF-κB transcription factor RelA is required for the tolerogenic function of Foxp3(+) regulatory T cells

J Autoimmun. 2016 Jun;70:52-62. doi: 10.1016/j.jaut.2016.03.017. Epub 2016 Apr 7.

Abstract

The properties of CD4(+) regulatory T cell (Treg) subsets are dictated by distinct patterns of gene expression determined by FOXP3 and different combinations of various transcription factors. Here we show the NF-κB transcription factor RelA is constitutively active in naïve and effector Tregs. The conditional inactivation of Rela in murine FOXP3(+) cells induces a rapid onset, multi-focal autoimmune disease that depends on RelA being expressed in conventional T cells. In addition to promoting Treg lineage stability, RelA determines the size of the effector Treg population, a function influenced by the presence or absence of RelA in conventional T cells. These findings showing that RelA controls Treg stability and promotes the competitive fitness of effector Tregs highlight the importance of RelA activity in peripheral Treg induced tolerance.

Keywords: Autoimmune disease; Conditional gene targeting; Nuclear factor of kappaB; Regulatory T cells; RelA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / blood
  • Antibodies / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Autoimmunity
  • Biomarkers
  • Cluster Analysis
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Immune Tolerance* / genetics
  • Immunomodulation
  • Immunophenotyping
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Transgenic
  • Phenotype
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*

Substances

  • Antibodies
  • Biomarkers
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Transcription Factor RelA