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

Journal Article · Fri Aug 17 04:00:00 EDT 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.07.065· OSTI ID:22210194

Doi, Keiko ^[1]; Fujimoto, Takahiro ^[1]; Okamura, Tadashi ^[2]; Ogawa, Masahiro ^[3]; Tanaka, Yoko ^[1]; Mototani, Yasumasa; Goto, Motohito ^[2]; Ota, Takeharu; Matsuzaki, Hiroshi ^[1]; Kuroki, Masahide ^[3]; Tsunoda, Toshiyuki ^[1]; Sasazuki, Takehiko ^[4]; Shirasawa, Senji ^[1]

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1. Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan)
2. Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan)
3. Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)
4. Institute for Advanced Study, Kyushu University, Fukuoka (Japan)

Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- 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-7R{alpha} 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-2R{alpha} 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.

• OSTI ID: 22210194
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 425; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
APOPTOSIS
BLOOD FORMATION
CELL PROLIFERATION
DISEASES
HOMEOSTASIS
LEAD
MICE
RECEPTORS
THYROID