Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
复制标题
DOI：
10.1038/382174a0
复制
发表时间：
1996-07-11
期刊：
影响因子：
64.8
通讯作者：
Grusby, MJ
中科院分区：
文献类型：
--
作者：
Kaplan, MH;Sun, YL;Grusby, MJ
细胞因子和受体之间的相互作用会导致多种信号分子的激活，包括信号转导蛋白和转录激活蛋白 (STAT) 蛋白家族(1,2)。 Stat4 是该家族的成员之一 (3,4)，并且仅在响应细胞因子白细胞介素 (IL)-12 时被激活（参考文献 5、6）。通过基因打靶，我们培育了 Stat4 缺陷的小鼠，以确定该转录因子的功能是否与 IL-12 激活的其他信号分子冗余。 IL-12 诱导的干扰素 (IFN)-γ 细胞增殖和自然杀伤 (NK) 细胞毒性的增加在 Statil 缺陷小鼠的淋巴细胞中被消除。在 Stat4 缺失的情况下，Th1 细胞对 IL-12 或单核细胞增生李斯特菌的反应也会受到损害。此外，Stat4 缺陷的淋巴细胞表现出 Th2 细胞发育的倾向。这些结果表明 Stat4 对于介导淋巴细胞对 IL-12 的反应以及调节 Th1 和 Th2 细胞的分化至关重要。
INTERACTIONS between cytokine and receptor lead to the activation of multiple signalling molecules, including the family of signal transducer and activator of transcription (STAT) proteins(1,2). Stat4 is one member of this family(3,4), and is activated only in response to the cytokine interleukin(IL)-12, (refs 5, 6). By gene targeting, we have generated mice deficient in Stat4 to determine whether the function of this transcription factor is redundant with other signalling molecules activated by IL-12. IL-12-induced increases in the production of interferon(IFN)-gamma cellular proliferation and natural killer (NK) cell cytotoxicity are abrogated in lymphocytes from Statil-deficient mice. The development of Th1 cells in response to either IL-12 or Listeria monocytogenes is also impaired in the absence of Stat4. Furthermore, Stat4-deficient lymphocytes demonstrate a propensity towards the development of Th2 cells. These results demonstrate that Stat4 is essential for mediating responses to IL-12 in lymphocytes, and regulating the differentiation of both Th1 and Th2 cells.