WNK1 kinase balances T cell adhesion versus migration in vivo

Nat Immunol. 2016 Sep;17(9):1075-83. doi: 10.1038/ni.3495. Epub 2016 Jul 11.

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.

MeSH terms

  • Animals
  • Cell Adhesion / genetics*
  • Cell Movement / genetics*
  • Cells, Cultured
  • Homeostasis
  • Ion Transport
  • Kidney / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / metabolism*
  • Solute Carrier Family 12, Member 2 / metabolism
  • T-Lymphocytes / physiology*
  • WNK Lysine-Deficient Protein Kinase 1

Substances

  • Minor Histocompatibility Antigens
  • Receptors, Lymphocyte Homing
  • Solute Carrier Family 12, Member 2
  • Stk39 protein, mouse
  • OXSR1 protein, mouse
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • Wnk1 protein, mouse