Kruppel-like factor 2 regulates thymocyte and T-cell migration
Kruppel-like factor 2 regulates thymocyte and T-cell migration
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DOI：
10.1038/nature04882
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发表时间：
2006-07-20
期刊：
影响因子：
64.8
通讯作者：
Jameson, Stephen C.
中科院分区：
文献类型：
--
作者：
Carlson, Corey M.;Endrizzi, Bart T.;Jameson, Stephen C.
哺乳动物的Kruppel类转录因子参与调节几种组织类型的末端分化(1-3)。缺乏Kruppel-like factor2(也称为LKLF)会导致外周T细胞库的大量丧失(4)，这表明KLF2调节T细胞的静止和存活(4-7)。然而，我们在这里展示了KLF2对于T细胞贩运是必不可少的。KLF2缺陷(KLF2(-/-))胸腺细胞表现出胸腺细胞迁移和外周运输所需的几种受体的表达受损，包括鞘氨醇-1-磷酸(S1P)受体S1P(1)、CD62L和β(7)整合素。此外，KLF2结合并反式激活S1P(1)的启动子，S1P(1)是胸腺细胞通过外周淋巴器官外出和再循环的关键受体。我们的发现表明，KLF2用于许可成熟T细胞从胸腺运输并通过次级淋巴组织再循环。
Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types(1-3). Deficiency in Kruppel-like factor (KLF) 2 ( also known as LKLF) leads to a massive loss of the peripheral T-cell pool(4), suggesting KLF2 regulates T-cell quiescence and survival(4-7). Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2(-/-)) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P(1), CD62L and beta(7) integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P(1) - a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.