Janus kinase 3 (Jak3) is essential for common cytokine receptor γ chain (γc)-dependent signaling:: comparative analysis of γc, Jak3, and γc and Jak3 double-deficient mice
Janus kinase 3 (Jak3) is essential for common cytokine receptor γ chain (γc)-dependent signaling:: comparative analysis of γc, Jak3, and γc and Jak3 double-deficient mice
复制标题
DOI：
10.1093/intimm/12.2.123
复制
发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Iwamoto, I
中科院分区：
文献类型：
--
作者：
Suzuki, K;Nakajima, H;Iwamoto, I
常见的细胞因子受体γ链（γ（c））是IL-2、IL-4、IL-7、IL-9和IL-15的必需受体组分，因此γ（c）缺陷小鼠表现出受损的T细胞和B细胞发育。已知Janus家族酪氨酸激酶3（Jak 3）与γ（c）相关，并且报道的γ（c）缺陷（γ（c）（-））和Jak 3缺陷（Jak 3（-））小鼠的表型相似，表明Jak 3是γ（c）依赖性信号的重要转导子。尽管如此，人们还是提出了与gamma（c）和Jak 3的作用范围相关的某些差异。为了澄清gamma（c）依赖性细胞因子在没有Jak 3的情况下是否可以部分转导其信号，我们比较了gamma（c）（-）、Jak 3（-）以及gamma（c）和Jak 3双缺陷（gamma（c）（-）Jak 3（-））小鼠的淋巴细胞发育在相同的遗传背景下。除了Jak 3-小鼠中的T和B细胞表达高水平的γ（c）外，胸腺细胞和外周T细胞和B细胞发育的缺陷在γ（c）（-）、Jak 3（-）和γ（c）（-）Jak 3（-）小鼠中无法区分。有趣的是，虽然Bcl-2诱导以前被认为是Jak 3独立的，但IL-7不能诱导γ（c）（-）或Jak 3（-）小鼠中CD 4单阳性（SP）胸腺细胞中的Bcl-2表达，IL-7也不能拯救γ（c）（-）或Jak 3（-）小鼠中地塞米松诱导的CD 4 SP胸腺细胞死亡。这些结果表明Jak 3对于γ（c）依赖性T细胞和B细胞发育以及γ（c）依赖性胸腺细胞凋亡的预防是绝对必要的。
The common cytokine receptor gamma chain (gamma(c)) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby gamma(c)-deficient mice exhibit impaired T cell and B cell development. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with gamma(c), and the reported phenotypes of gamma(c)-deficient (gamma(c)(-)) and Jak3-deficient (Jak3(-)) mice are similar, indicating that Jak3 is an essential transducer of gamma(c)-dependent signals. Nevertheless, certain differences have been suggested related to the range of actions of gamma(c) and Jak3, To clarify whether gamma(c)-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in gamma(c)(-), Jak3(-), and gamma(c) and Jak3 double-deficient (gamma(c)(-)Jak3(-)) mice in the same genetic background. With the exception that T and B cells in Jak3- mice express high levels of gamma(c), the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among gamma(c)(-), Jak3(-) and gamma(c)(-)Jak3(-) mice. Interestingly, although Bcl-2 induction was previously suggested to be Jak3-independent, IL-7 cannot induce Bcl-2 expression in CD4 single-positive (SP) thymocytes in either gamma(c)(-) or Jak3(-) mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in gamma(c)(-) or Jak3(-) mice. These results indicate that Jak3 is absolutely essential for gamma(c)-dependent T cell and B cell development, and for gamma(c)-dependent prevention of thymocyte apoptosis.