The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity

Nat Commun. 2014 Oct 10:5:5225. doi: 10.1038/ncomms6225.

Abstract

T-cell activation is critical for successful immune responses and is controlled at multiple levels. Although many changes of T-cell receptor-associated signalling molecules affect T-cell activation, the transcriptional mechanisms that control this process remain largely unknown. Here we find that T cell-specific deletion of the mediator subunit Med23 leads to hyperactivation of T cells and aged Med23-deficient mice exhibit an autoimmune syndrome. Med23 specifically and consistently promotes the transcription of multiple negative regulators of T-cell activation. In the absence of Med23, the T-cell activation threshold is lower, which results in enhanced antitumour T-cell function. Cumulatively, our data suggest that Med23 contributes to controlling T-cell activation at the transcriptional level and prevents the development of autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Female
  • Lymphocyte Activation
  • Male
  • Mediator Complex / genetics
  • Mediator Complex / immunology*
  • Mice
  • Mice, Knockout
  • T-Lymphocytes / immunology*
  • Transcription, Genetic

Substances

  • Med23 protein, mouse
  • Mediator Complex

Associated data

  • GEO/GSE60779