Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice
Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice
复制标题
DOI：
10.1016/s1074-7613(00)80253-8
复制
发表时间：
1996-04-01
期刊：
影响因子：
32.4
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
Hodge, MR;Ranger, AM;Glimcher, LH
核因子-三磷酸腺苷是编码活化T细胞核因子胞浆成分的基因家族的一员。在这项研究中，我们发现NF-ATP基因零突变的小鼠脾肿大，B细胞和T细胞均过度增殖。它们还显示出编码细胞因子和细胞表面受体的多个基因的早期转录缺陷，包括CD40L和Fast。在体内用抗CD3抗体处理TCR复合体后，早期IL-4的产生出现了显著的缺陷。其他细胞因子包括IL-13、GM-CSF和肿瘤坏死因子α的转录也受到影响，尽管程度较小。有趣的是，细胞因子IL-2和干扰素-γ受到的影响很小。尽管存在IL-4转录的早期缺陷，但Th2的发育实际上在后来的时间点得到了促进，这一点从IL-4的产生和IgE水平的增加可见一斑，在体外和体内都有利于Th2细胞的形成。这些数据表明，核因子-ATP可能参与细胞生长，并在免疫反应过程中对IL-4基因的平衡转录很重要。
NF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and Fast. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFN gamma were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.