WNK1 kinase balances T cell adhesion versus migration in vivo

R Köchl, F Thelen, L Vanes, TF Brazão, K Fountain… - Nature …, 2016 - nature.com
R Köchl, F Thelen, L Vanes, TF Brazão, K Fountain, J Xie, CL Huang, R Lyck, JV Stein
Nature immunology, 2016nature.com
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 …
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.
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