title: TRIM28 prevents autoinflammatory T cell development in vivo.
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.
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Chikuma
authors.forename: Naomasa
authors.initials: N
authors.lastname: Suita
authors.forename: Il-Mi
authors.initials: IM
authors.lastname: Okazaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Shibayama
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology*; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D058504:Th17 Cells / Q000276:immunology; D053782:Transforming Growth Factor beta3 / Q000096:biosynthesis / Q000276:immunology*; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; D053782:Transforming Growth Factor beta3; D004247:DNA; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28