WNK1 kinase balances T cell adhesion versus migration in vivo

Robert Köchl; Flavian Thelen; Lesley Vanes; Tiago F Brazão; Kathryn Fountain; Jian Xie; Chou-Long Huang; Ruth Lyck; Jens V Stein; Victor L J Tybulewicz

doi:10.1038/ni.3495

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WNK1 kinase balances T cell adhesion versus migration in vivo

Journal article

Peer reviewed

WNK1 kinase balances T cell adhesion versus migration in vivo

Robert Köchl, Flavian Thelen, Lesley Vanes, Tiago F Brazão, Kathryn Fountain, Jian Xie, Chou-Long Huang, Ruth Lyck, Jens V Stein and Victor L J Tybulewicz

Nature immunology, Vol.17(9), pp.1075-1083

09/2016

DOI: 10.1038/ni.3495

PMCID: PMC4994873

PMID: 27400149

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https://kclpure.kcl.ac.uk/portal/en/publications/6ddedb5c-7886-4102-a7ce-ba933bb960a1View

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Abstract

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.

Receptors, Lymphocyte Homing - genetics

Solute Carrier Family 12, Member 2 - metabolism

T-Lymphocytes - physiology

Cell Adhesion - genetics

Mice, Inbred C57BL

Cells, Cultured

Protein-Serine-Threonine Kinases - genetics

Homeostasis

Receptors, Lymphocyte Homing - metabolism

Cell Movement - genetics

Mice, Knockout

Transcription Factors - metabolism

Kidney - metabolism

Minor Histocompatibility Antigens - metabolism

Animals

WNK Lysine-Deficient Protein Kinase 1

RNA Interference

Minor Histocompatibility Antigens - genetics

Ion Transport

Mice

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: WNK1 kinase balances T cell adhesion versus migration in vivo
Creators: Robert Köchl - The Francis Crick Institute, London, UK
Flavian Thelen - Theodor Kocher Institute, University of Bern, Bern, Switzerland
Lesley Vanes - The Francis Crick Institute, London, UK
Tiago F Brazão - The Francis Crick Institute, London, UK
Kathryn Fountain - The Francis Crick Institute, London, UK
Jian Xie - University of Texas Southwestern Medical Center, Dallas, Texas, USA
Chou-Long Huang - University of Texas Southwestern Medical Center, Dallas, Texas, USA
Ruth Lyck - Theodor Kocher Institute, University of Bern, Bern, Switzerland
Jens V Stein - Theodor Kocher Institute, University of Bern, Bern, Switzerland
Victor L J Tybulewicz - Department of Medicine, Imperial College, London, UK
Resource Type: Journal article
Publication Details: Nature immunology, Vol.17(9), pp.1075-1083
DOI: 10.1038/ni.3495
PMID: 27400149
PMCID: PMC4994873
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Grant note: Cancer Research UK Wellcome Trust P30 DK079307 / NIDDK NIH HHS 089185 / Wellcome Trust R01 DK059530 / NIDDK NIH HHS BB/L00805X/1 / Biotechnology and Biological Sciences Research Council MC_U117527252 / Medical Research Council
Language: English
Date published: 09/2016
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094210402771

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WNK1 kinase balances T cell adhesion versus migration in vivo

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