UXT is a novel regulatory factor of regulatory T cells associated with Foxp3

Eur J Immunol. 2014 Feb;44(2):533-44. doi: 10.1002/eji.201343394. Epub 2013 Nov 29.

Abstract

Regulatory T (Treg) cells are a constitutively immunosuppressive subtype of T cells that contribute to the maintenance of immunological self-tolerance and immune homeostasis. However, the molecular mechanisms involved in the regulation of Treg cells remain unclear. In the present study, we identified ubiquitously expressed transcript (UXT) to be a novel regulator of human Treg-cell function. In cultured human Treg cells, UXT associates with Foxp3 in the nucleus by interacting with the proline-rich domain in the N-terminus of Foxp3. Knockdown of UXT expression in Treg cells results in a less-suppressive phenotype, demonstrating that UXT is an important regulator of the suppressive actions of Treg cells. Depletion of UXT affects the localization stability of Foxp3 protein in the nucleus and downregulates the expression of Foxp3-related genes. Overall, our results show that UXT is a cofactor of Foxp3 and an important player in Treg-cell function.

Keywords: Cofactor; Foxp3; Immune suppression; Regulatory T (Treg) cell; UXT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism*
  • HEK293 Cells
  • Humans
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Molecular Chaperones
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Proline / genetics
  • Proline / immunology
  • Proline / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology
  • Yeasts / genetics
  • Yeasts / immunology
  • Yeasts / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Molecular Chaperones
  • Neoplasm Proteins
  • UXT protein, human
  • Proline