WNK1 kinase balances T cell adhesion versus migration in vivo
journal contributionposted on 2020-08-12, 13:40 authored by Robert Köchl, Flavian Thelen, Lesley Vanes, Tiago F Brazão, Kathryn Fountain, Jian Xie, Chou-Long Huang, Ruth Lyck, Jens V Stein, Victor LJ Tybulewicz
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.
AnimalsCell AdhesionCell MovementCells, CulturedHomeostasisIon TransportKidneyMiceMice, Inbred C57BLMice, KnockoutMinor Histocompatibility AntigensProtein-Serine-Threonine KinasesRNA InterferenceReceptors, Lymphocyte HomingSolute Carrier Family 12, Member 2T-LymphocytesTranscription FactorsWNK Lysine-Deficient Protein Kinase 1Tybulewicz FC001194Immunology1107 Immunology