ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

Keiko Doi, Takahiro Fujimoto, Tadashi Okamura, Masahiro Ogawa, Yoko Tanaka, Yasumasa Mototani, Motohito Goto, Takeharu Ota, Hiroshi Matsuzaki, Masahide Kuroki, Toshiyuki Tsunoda, Takehiko Sasazuki, Senji Shirasawa

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11 Citations (Scopus)

Abstract

ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number1
DOIs
Publication statusPublished - Aug 17 2012

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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