Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing
Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing
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DOI：
10.1016/j.immuni.2004.07.012
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发表时间：
2004-09-01
期刊：
影响因子：
32.4
通讯作者：
Stein, JV
中科院分区：
文献类型：
--
作者：
Nombela-Arrieta, C;Lacalle, RA;Stein, JV
趋化因子通过触发血管流动下的整合素依赖性牢固粘附和淋巴组织内T和B淋巴细胞的定向迁移，将淋巴细胞从血液引导至次级淋巴器官。在这里，我们分析DOCK 2，秀丽隐杆线虫CED-5和果蝇成肌细胞城的哺乳动物同源物，和磷酸肌醇-3-激酶（PI 3 K）在淋巴细胞再循环过程中的作用。DOCK 2介导的有效淋巴细胞迁移在很大程度上PI 3 K非依赖性的方式，虽然一个小的，PI 3 K依赖性的迁移途径中观察到野生型和DOCK 2缺陷的淋巴细胞。在T细胞中，这种残留迁移主要依赖于PI 3 K γ，而其他PI 3 K亚型与B细胞有关。淋巴器官脉管系统的体外粘附测定和活体显微镜检查揭示了DOCK 2（-/-）B细胞中整合素活化的意外缺陷，而缺乏DOCK 2并不影响T细胞中趋化因子触发的整合素活化。因此，DOCK 2和PI 3 K γ在T和B细胞整联蛋白活化和迁移过程中发挥不同的作用。
Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kgamma, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2(-/-) B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kgamma thus play distinct roles during T and B cell integrin activation and migration.