Role of DOCK2 and DOCK180 in fetal thymus colonization
Role of DOCK2 and DOCK180 in fetal thymus colonization
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DOI：
10.1002/eji.200939630
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Lei, Yu;Liu, Cunlan;Takahama, Yousuke
胎儿胸腺定植在胸腺原基血管化之前开始。 T 淋巴细胞祖细胞对胎儿胸腺的血管前定植是由 CCR7 和 CCR9 介导的趋化因子信号的协调引导的。然而，介导 T 淋巴祖细胞血管前迁移至胎儿胸腺的细胞内信号尚不清楚。在这里，我们发现胎儿小鼠的 T 淋巴细胞祖细胞表达两个密切相关的 CDM 家族分子：DOCK2 和 DOCK180。我们发现，在 DOCK2 和 DOCK180 双缺陷的小鼠中，血管前胎儿胸腺体内积累显着减少，但在 DOCK2 或 DOCK180 缺陷的小鼠中则没有。来自 DOCK2 和 DOCK180 双缺陷小鼠的未成熟 T 淋巴细胞在体外向胎儿胸腺叶迁移方面存在缺陷。缺乏DOCK2和DOCK180的小鼠中产生的T淋巴细胞在转移到胎儿胸腺环境后能够发育为T细胞，并且缺乏DOCK2和DOCK180的小鼠中胎儿胸腺定植受损的情况不像CCR7和CCR9双缺陷的小鼠那么严重。这些结果表明DOCK2和DOCK180的组合在血管前胎儿胸腺定植中发挥显着但非必需的作用。
Fetal thymus colonization is initiated before the vascularization of the thymus primordium. This prevascular colonization of the fetal thymus by T-lymphoid progenitor cells is guided by the coordination of CCR7- and CCR9-mediated chemokine signals. However, the intracellular signals that mediate the prevascular migration of T-lymphoid progenitor cells to the fetal thymus are unknown. Here we show that T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, DOCK2 and DOCK180. We found that the prevascular fetal thymus accumulation in vivo was significantly reduced in mice doubly deficient for DOCK2 and DOCK180 but not in mice deficient for either DOCK2 or DOCK180. Immature T-lymphoid cells from mice doubly deficient for DOCK2 and DOCK180 were defective in their in vitro migration towards fetal thymus lobes. The T-lymphoid progenitor cells generated in mice lacking DOCK2 and DOCK180 were capable of T-cell development after their transfer into a fetal thymus environment, and the impaired fetal thymus colonization in mice deficient for DOCK2 and DOCK180 was not as severe as that in mice doubly deficient for CCR7 and CCR9. These results indicate that the combination of DOCK2 and DOCK180 plays a significant but not essential role in prevascular fetal thymus colonization.