Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells

Nat Immunol. 2012 May;13(5):481-90. doi: 10.1038/ni.2267.

Abstract

The maintenance of immune homeostasis requires regulatory T cells (Treg cells). Here we found that Treg cell–specific ablation of Ubc13, a Lys63 (K63)-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect the survival of Treg cells or expression of the transcription factor Foxp3, it impaired the in vivo suppressive function of Treg cells and rendered them sensitive to the acquisition of T helper type 1 (TH1) cell– and interleukin 17 (IL-17)-producing helper T (TH17) cell–like effector phenotypes. This function of Ubc13 involved its downstream target, the kinase IKK. The Ubc13-IKK signaling axis controlled the expression of specific Treg cell effector molecules, including IL-10 and SOCS1. Collectively, our findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains Treg cell function and prevents Treg cells from acquiring inflammatory phenotypes.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Differentiation / immunology*
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • I-kappa B Kinase / deficiency
  • I-kappa B Kinase / immunology
  • I-kappa B Kinase / metabolism*
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction / immunology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Ubiquitin-Conjugating Enzymes / deficiency
  • Ubiquitin-Conjugating Enzymes / immunology*
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interleukin-10
  • Ube2n protein, mouse
  • Ubiquitin-Conjugating Enzymes
  • I-kappa B Kinase