WNK1 kinase balances T cell adhesion versus migration in vivo

被引：53

作者：

Kochl, Robert ^{[1
]}

Thelen, Flavian ^{[2
]}

Vanes, Lesley ^{[1
]}

Brazao, Tiago F. ^{[1
]}

Fountain, Kathryn ^{[1
]}

Xie, Jian ^{[3
]}

Huang, Chou-Long ^{[3
]}

Lyck, Ruth ^{[2
]}

Stein, Jens V. ^{[2
]}

Tybulewicz, Victor L. J. ^{[1
,4
]}

机构：

[1] Francis Crick Inst, London, England

[2] Univ Bern, Theodor Kocher Inst, Bern, Switzerland

[3] Univ Texas Southwestern Med Ctr, Dallas, TX USA

[4] Imperial Coll, Dept Med, London, England

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 09期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

INTEGRIN ACTIVATION; LEUKOCYTE MIGRATION; PROTEIN-KINASES; BLOOD-PRESSURE; ROLES; LFA-1; MICE; COTRANSPORTER; EXPRESSION; REGULATOR;

D O I：

10.1038/ni.3495

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.

引用

收藏

页码：1075 / 1083

页数：9

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