title: WNK1 kinase balances T cell adhesion versus migration in vivo.
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.
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Köchl
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Flavian
authors.initials: F
authors.lastname: Thelen
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Tiago F
authors.initials: TF
authors.lastname: Brazão
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Fountain
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xie
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Chou-Long
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lyck
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
authors.affiliation: The Francis Crick Institute, London, UK.|Department of Medicine, Imperial College, London, UK.
authors.forename: Victor L J
authors.identifier: 0000-0003-2439-0798
authors.initials: VL
authors.lastname: Tybulewicz
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D006706:Homeostasis; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D015778:Minor Histocompatibility Antigens; D016201:Receptors, Lymphocyte Homing; D064506:Solute Carrier Family 12, Member 2; C486407:Stk39 protein, mouse; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse