Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells
Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells
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DOI：
10.1189/jlb.2a0814-384r
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发表时间：
2015-09-01
影响因子：
5.5
通讯作者：
Muta, Tatsushi
中科院分区：
文献类型：
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作者：
MaruYama, Takashi;Kobayashi, Shuhei;Muta, Tatsushi
转录调控因子I kappa B-Zeta在角质形成细胞的凋亡调控中起着重要作用。因此，I kappa B-Zeta缺陷小鼠会患上自身免疫性疾病，如干燥综合征。然而，T细胞在干燥综合征中也起着关键作用。为了研究I kappa B-Zeta在T细胞中的作用，我们培育了T细胞特异性的I kappa B-Zeta缺陷小鼠。我们观察到3周龄小鼠的外周效应/记忆CD4(+)细胞和产生干扰素-γ的CD4(+)细胞数量增加。我们发现I-kappa B-Zeta可以被转化生长因子-β1上调初始的CD4(+)T细胞，并负向调节干扰素-γ的表达。此外，我们还建立了T-reg特异性的I kappa B-Zeta缺陷小鼠，发现I kappa B-Zeta对于T-regs的可塑性和稳定性是必不可少的。然而，来自T细胞特异性的T-regs，I kappa B-zeta缺陷小鼠的免疫调节功能降低。因此，我们的数据揭示了I kappa B-Zeta在T细胞产生干扰素-γ和T-regs的免疫调节功能中以前未被认识到的作用。
The transcriptional regulator I kappa B-zeta is important for the control of apoptosis in keratinocytes. Thus, I kappa B-zeta-deficient mice develop autoimmune diseases, such as Sjogren's syndrome. However, T cells also play a pivotal role in Sjogren's syndrome. To study the role of I kappa B-zeta in T cells, we generated T cell-specific, I kappa B-zeta-deficient mice. We observed increased numbers of peripheral effector/memory CD4(+) cells and IFN-gamma-producing CD4(+) cells in 3-week-old mice. We found that I kappa B-zeta can be up-regulated by TGF-beta 1 in naive CD4(+) T cells and that it negatively regulates IFN-gamma expression. In addition, we generated T-reg-specific, I kappa B-zeta deficient mice and found that I kappa B-zeta is dispensable for the plasticity and stability of T-regs. However, T-regs from T cell-specific, I kappa B-zeta-deficient mice have reduced immunoregulatory function. Thus, our data reveal a previously unappreciated role for I kappa B-zeta in IFN-gamma production in T cells and the immunoregulatory function of T-regs.