WNK1 kinase balances T cell adhesion versus migration in vivo

  • Nat Immunol. 2016 Sep;17(9):1075-83. doi: 10.1038/ni.3495.
Robert Köchl  1 ,  Flavian Thelen  2 ,  Lesley Vanes  1 ,  Tiago F Brazão  1 ,  Kathryn Fountain  1 ,  Jian Xie  3 ,  Chou-Long Huang  3 ,  Ruth Lyck  2 ,  Jens V Stein  2 ,  Victor L J Tybulewicz  1  4
Affiliations
  • 1. The Francis Crick Institute, London, UK.
  • 2. Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • 3. University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • 4. Department of Medicine, Imperial College, London, UK.
PMID: 27400149 DOI: 10.1038/ni.3495
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.