TY - JOUR
T1 - ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response
AU - Doi, Keiko
AU - Fujimoto, Takahiro
AU - Okamura, Tadashi
AU - Ogawa, Masahiro
AU - Tanaka, Yoko
AU - Mototani, Yasumasa
AU - Goto, Motohito
AU - Ota, Takeharu
AU - Matsuzaki, Hiroshi
AU - Kuroki, Masahide
AU - Tsunoda, Toshiyuki
AU - Sasazuki, Takehiko
AU - Shirasawa, Senji
N1 - Funding Information:
The authors thank Hiroshi Takamoto, Takashi Machida, Koutarou Tsutsumi, Yuko Yoshimura and Takami Danno for technical assistance. This work was supported in part by a Scientific Research (B) from the Japan Society for the Promotion of the Science and a Grant-in-Aid for the FCAM from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities.
PY - 2012/8/17
Y1 - 2012/8/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2012.07.065
DO - 10.1016/j.bbrc.2012.07.065
M3 - Article
C2 - 22828507
AN - SCOPUS:84865186592
SN - 0006-291X
VL - 425
SP - 107
EP - 112
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -