CREB function is required for normal thymic cellularity and post-irradiation recovery
CREB function is required for normal thymic cellularity and post-irradiation recovery
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DOI：
10.1002/eji.200324826
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发表时间：
2004-07-01
影响因子：
5.4
通讯作者：
Mantamadiotis, T
中科院分区：
文献类型：
--
作者：
Baumann, S;Kyewski, B;Mantamadiotis, T
最近一代基因修饰的Creb1突变小鼠揭示了CREB （CAMP响应元件结合蛋白）及其相关蛋白CREM （CAMP响应元件调节剂）和ATF1（激活转录因子1）在细胞存活中的重要作用，这与先前使用显性阴性CREB （dnCREB）过表达的研究一致。CREB和ATF1在T细胞中大量表达，当T细胞通过T细胞抗原受体受到刺激时，它们被迅速磷酸化激活。我们发现，小鼠中T细胞特异性CREB的缺失，加上ATF1的缺失，导致胸腺细胞数量减少和亚致死照射后胸腺恢复延迟，但T细胞的发育或激活没有变化。这些数据表明，CREB功能的丧失对体内胸腺T淋巴细胞增殖和稳态具有特异性影响。
Recent generation of genetically modified Creb1 mutant mice has revealed an important role for CREB (CAMP responsive element binding protein) and the related proteins CREM (CAMP responsive element modulator) and ATF1 (activating transcription factor 1) in cell survival, in agreement with previous studies using overexpression of dominant-negative CREB (dnCREB). CREB and ATF1 are abundantly expressed in T cells and are rapidly activated by phosphorylation when T cells are stimulated through the T cell antigen receptor. We show that T cell-specific loss of CREB in mice, in combination with the loss of ATF1, results in reduced thymic cellularity and delayed thymic recovery following sublethal irradiation but no changes in T cell development or activation. These data show that loss of CREB function has specific effects on thymic T lymphocyte proliferation and homeostasis in vivo.