WNK1 kinase balances T cell adhesion versus migration in vivo

• Published in: Nature immunology Vol. 17; no. 9; pp. 1075 - 1083
• Main Authors: Köchl, Robert, Thelen, Flavian, Vanes, Lesley, Brazão, Tiago F, Fountain, Kathryn, Xie, Jian, Huang, Chou-Long, Lyck, Ruth, Stein, Jens V, Tybulewicz, Victor L J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2016; Nature Publishing Group
• Subjects: 13; 13/31; 13/95; 14; 14/69; 38/91; 631/250/1619/554; 631/250/516; 631/80/84/1372; 64; 64/110; 64/60; Adhesion; Animals; Biomedicine; Cell adhesion; Cell Adhesion - genetics; Cell migration; Cell Movement - genetics; Cells, Cultured; Genetic aspects; Health aspects; Homeostasis; Immunology; Infectious Diseases; Ion Transport; Kidney - metabolism; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - metabolism; Phosphotransferases; Properties; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Receptors, Lymphocyte Homing - genetics; Receptors, Lymphocyte Homing - metabolism; RNA Interference; Solute Carrier Family 12, Member 2 - metabolism; T-Lymphocytes - physiology; WNK Lysine-Deficient Protein Kinase 1
• DOI: 10.1038/ni.3495
• ISSN: 1529-2908

The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1 also operates in T cells, in which it negatively regulates adhesion and positively regulates migration. 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.