MaruYama Takashi, Kobayashi Shuhei, Ogasawara Kouetsu, Yoshimura Akihiko, Chen WanJun, Muta Tatsushi
*Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
*Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
J Leukoc Biol. 2015 Sep;98(3):385-93. doi: 10.1189/jlb.2A0814-384R. Epub 2015 May 27.
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(+) cells and IFN-γ-producing CD4(+) cells in 3-week-old mice. We found that IκB-ζ can be up-regulated by TGF-β1 in naïve CD4(+) 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 Tregs. However, Tregs 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 Tregs.
转录调节因子IκB-ζ对于控制角质形成细胞的凋亡至关重要。因此，IκB-ζ基因缺陷型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IκB-ζ在T细胞中的作用，我们构建了T细胞特异性IκB-ζ基因缺陷型小鼠。我们观察到3周龄小鼠外周效应/记忆CD4(+)细胞和产生IFN-γ的CD4(+)细胞数量增加。我们发现IκB-ζ可被初始CD4(+) T细胞中的TGF-β1上调，并且它对IFN-γ表达起负调节作用。此外，我们构建了调节性T细胞（Treg）特异性IκB-ζ基因缺陷型小鼠，发现IκB-ζ对于Treg的可塑性和稳定性并非必需。然而，来自T细胞特异性IκB-ζ基因缺陷型小鼠的Treg免疫调节功能降低。因此，我们的数据揭示了IκB-ζ在T细胞IFN-γ产生及Treg免疫调节功能中一个此前未被认识到的作用。
