TRIM28 prevents autoinflammatory T cell development in vivo

Shunsuke Chikuma, Naomasa Suita, Il Mi Okazaki, Shiro Shibayama, Tasuku Honjo

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 H17 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.

Original languageEnglish
Pages (from-to)596-603
Number of pages8
JournalNature Immunology
Volume13
Issue number6
DOIs
Publication statusPublished - 2012 Jun
Externally publishedYes

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T-Lymphocytes
Cytokines
Phenotype
Lymphopenia
Heterochromatin
T-Lymphocyte Subsets
Helper-Inducer T-Lymphocytes
T-Cell Antigen Receptor
Interleukin-2
Immune System
Cell Cycle

ASJC Scopus subject areas

  • Immunology

Cite this

Chikuma, S., Suita, N., Okazaki, I. M., Shibayama, S., & Honjo, T. (2012). TRIM28 prevents autoinflammatory T cell development in vivo. Nature Immunology, 13(6), 596-603. https://doi.org/10.1038/ni.2293

TRIM28 prevents autoinflammatory T cell development in vivo. / Chikuma, Shunsuke; Suita, Naomasa; Okazaki, Il Mi; Shibayama, Shiro; Honjo, Tasuku.

In: Nature Immunology, Vol. 13, No. 6, 06.2012, p. 596-603.

Research output: Contribution to journalArticle

Chikuma, S, Suita, N, Okazaki, IM, Shibayama, S & Honjo, T 2012, 'TRIM28 prevents autoinflammatory T cell development in vivo', Nature Immunology, vol. 13, no. 6, pp. 596-603. https://doi.org/10.1038/ni.2293
Chikuma, Shunsuke ; Suita, Naomasa ; Okazaki, Il Mi ; Shibayama, Shiro ; Honjo, Tasuku. / TRIM28 prevents autoinflammatory T cell development in vivo. In: Nature Immunology. 2012 ; Vol. 13, No. 6. pp. 596-603.
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