TRIM28 prevents autoinflammatory T cell development in vivo

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

Research output: Contribution to journalArticle

67 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 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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