Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells

Takashi MaruYama, Shuhei Kobayashi, Kouetsu Ogasawara, Akihiko Yoshimura, WanJun Chen, Tatsushi Muta

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The transcriptional regulator IκB-ζ is important for the control of apoptosis in keratinocytes. Thus, IκB-ζ-deficient mice develop autoimmune diseases, such as Sjögren’s syndrome. However, T cells also play a pivotal role in Sjögren’s syndrome. To study the role of IκB-ζ in T cells, we generated T cell-specific, IκB-ζ-deficient mice. We observed increased numbers of peripheral effector/memory CD4<sup>+</sup> cells and IFN-γ-producing CD4<sup>+</sup> cells in 3-week-old mice. We found that IκB-ζ can be up-regulated by TGF-β1 in naïve CD4<sup>+</sup> T cells and that it negatively regulates IFN-γ expression. In addition, we generated Treg-specific, IκB-ζ deficient mice and found that IκB-ζ is dispensable for the plasticity and stability of T<inf>regs</inf>. However, T<inf>regs</inf> from T cell-specific, IκB-ζ-deficient mice have reduced immunoregulatory function. Thus, our data reveal a previously unappreciated role for IκB-ζ in IFN-γ production in T cells and the immunoregulatory function of T<inf>regs</inf>.

Original languageEnglish
Pages (from-to)385-393
Number of pages9
JournalJournal of Leukocyte Biology
Volume98
Issue number3
DOIs
Publication statusPublished - 2015 Sep 1

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Keywords

  • Cytokine
  • T lymphocyte
  • Transcriptional regulator

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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