WNK1 kinase balances T cell adhesion versus migration in vivo.
WNK1 kinase balances T cell adhesion versus migration in vivo.
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DOI：
10.1038/ni.3495
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发表时间：
2016-09
影响因子：
30.5
通讯作者：
Tybulewicz VL
中科院分区：
文献类型：
--
作者：
Köchl R;Thelen F;Vanes L;Brazão TF;Fountain K;Xie J;Huang CL;Lyck R;Stein JV;Tybulewicz VL
T细胞的黏附和迁移受趋化因子和黏附分子，尤其是整合素的调控，对T淋巴细胞的正常生理功能起着至关重要的作用。利用RNA干扰筛选，我们已经确定WNK1激酶是整合素介导的黏附和T细胞迁移的调节因子。我们证明WNK1是整合素介导的黏附的负调节因子，而它通过OXSR1和STK39激酶以及SLc12a2离子共转运蛋白发挥正调节迁移的作用。缺乏WNK1的T细胞在淋巴器官中的归宿效率较低，在淋巴器官中的迁移速度也较慢。我们的结果表明，迄今已知的一种途径只调节肾脏中的盐平衡，以平衡T细胞的黏附和迁移。
Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and play critical roles in the normal physiological function of T lymphocytes. Using an RNA interference screen we have identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We demonstrate that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter. WNK1-deficient T cells home less efficiently to lymphoid organs, and migrate more slowly through them. Our results reveal that a pathway hitherto known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.