TRIM28 prevents autoinflammatory T cell development in vivo

Shunsuke Chikuma; Naomasa Suita; Il-Mi Okazaki; Shiro Shibayama; Tasuku Honjo

doi:10.1038/ni.2293

TRIM28 prevents autoinflammatory T cell development in vivo

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

Authors

Shunsuke Chikuma¹, Naomasa Suita, Il-Mi Okazaki, Shiro Shibayama, Tasuku Honjo

Affiliation

¹ Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

PMID: 22544392
DOI: 10.1038/ni.2293

Abstract

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

Substances

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