TRIM28 prevents autoinflammatory T cell development in vivo

Nat Immunol. 2012 Apr 29;13(6):596-603. doi: 10.1038/ni.2293.


TRIM28 is a component of heterochromatin complexes whose function in the immune system is unknown. By studying mice with conditional T cell-specific deletion of TRIM28 (CKO mice), we found that TRIM28 was phosphorylated after stimulation via the T cell antigen receptor (TCR) and was involved in the global regulation of CD4(+) T cells. The CKO mice had a spontaneous autoimmune phenotype that was due in part to early lymphopenia associated with a defect in the production of interleukin 2 (IL-2) as well as incomplete cell-cycle progression of their T cells. In addition, CKO T cells showed derepression of the cytokine TGF-β3, which resulted in an altered cytokine balance; this caused the accumulation of autoreactive cells of the T(H)17 subset of helper T cells and of Foxp3(+) T cells. Notably, CKO Foxp3(+) T cells were unable to prevent the autoimmune phenotype in vivo. Our results show critical roles for TRIM28 in both T cell activation and T cell tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Cycle / immunology*
  • DNA / chemistry
  • DNA / genetics
  • Forkhead Transcription Factors / immunology
  • Humans
  • Inflammation / immunology
  • Interleukin-2 / blood
  • Interleukin-2 / immunology*
  • Jurkat Cells
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Specific Pathogen-Free Organisms
  • Th17 Cells / immunology
  • Transforming Growth Factor beta3 / biosynthesis
  • Transforming Growth Factor beta3 / immunology*
  • Tripartite Motif-Containing Protein 28


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Repressor Proteins
  • Transforming Growth Factor beta3
  • DNA
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28

Associated data

  • GEO/GSE32224