WNK1 kinase balances T cell adhesion versus migration in vivo

Journal Article: Nature ImmunologyYear Published: (2016) Volume Number: 17, Article Number: 1075-1083


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

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.