WNK1 kinase balances T cell adhesion versus migration in vivo

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.