Cutting edge:: Role of STAT1, STAT3, and STAT5 IFN-αβ responses in T lymphocytes
Cutting edge:: Role of STAT1, STAT3, and STAT5 IFN-αβ responses in T lymphocytes
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DOI：
10.4049/jimmunol.174.2.609
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
David, M
中科院分区：
文献类型：
--
作者：
Tanabe, Y;Nishibori, T;David, M
IFN-α受体的参与启动了多个信号级联，包括STAT的激活。在这项研究中，我们证明了IFN-α B，尽管在野生型CD 4（+）或CD 8（+）T细胞中具有抗增殖作用，但在其STAT 1（- /-）对应物中充当强有丝分裂原。此外，IFN-α在野生型细胞中对细胞凋亡几乎没有影响，但在没有STAT 1的情况下是有效的存活因子。在没有STAT 1的情况下，抗凋亡反应主要由STAT 3介导，并且在较小程度上由STAT 5A/B介导。相比之下，当STAT 5AIB表达也被废除时，通过缺乏STAT 1获得的促有丝分裂IFN-α应答仅受到轻微影响，但完全依赖于STAT 3激活。这些发现为STAT 3和STAT 5A/B在IFN-α应答中的功能提供了第一个证据，并支持IFN-α受体分别通过STAT 1、STAT 3和STAT 5A/B启动促凋亡和抗凋亡应答的模型。
Engagement of the IFN-alphabeta receptor initiates multiple sig- naling cascades, including activation of the STAT In this study, we demonstrate that IFN-alphaB, although antiproliferative in wild-type CD4(+) or CD8(+) T cells, act as strong mitogens on their STAT1(- /-) counterparts. Furthermore, IFN-alphabeta exert little effect on apoptosis in wild-type cells, but are potent survival factors in the absence of STAT1. The antiapoptotic response in the absence of STAT1 is predominantly mediated by STAT3, and to a lesser extent by STAT5A/B. In contrast, the mitogenic IFN-alphabeta response gained through the absence of STAT1 is only marginally affected when STAT5AIB expression is also abrogated, but is completely dependent on STAT3 activation. These findings provide the first evidence for a function of STAT3 and STAT5A/B in the IFN-alphabeta response, and support a model in which the IFN-alphabeta receptor initiates both pro- and antiapoptotic responses through STAT1, and STAT3 and STAT5A/B, respectively.