Immune cells images with help from the Crick's Light Microscopy STP.

Introduction

Migration and adhesion are critical for the physiology of B and T lymphocytes. Using an RNAi screen, we identified a novel pathway involving the WNK1 kinase that regulates both adhesion and migration.

B and T cell migration and adhesion.

Figure 1: The WNK1 pathway. WNK1 transduces TCR and CCR7 signals leading to negative regulation of the RAP1 GTPase and LFA1-mediated adhesion. WNK1 also transduces CCR7 signals leading to migration via OSR1, SPAK and NKCC1.

Migration and adhesion are critical for the physiology of B and T lymphocytes. Using an RNAi screen, we identified a novel pathway involving the WNK1 kinase that regulates both adhesion and migration. We showed that WNK1 is a negative regulator of TCR- and chemokine-induced adhesion through the LFA1 integrin in T cells. Our work showed that WNK1 negatively regulates LFA1 via the RAP1 GTPase. In addition, WNK1 is a positive regulator of chemokine-induced T cell migration. In this process it acts via the OXSR1 (OSR1) and STK39 (SPAK) kinases to phosphorylate SLC12A2 (NKCC1) thereby allowing Na+, K+ and Cl- ions to enter the cell.

More recently we have shown the WNK1 is also a negative regulator of adhesion and a positive regulator of migration in B cells. Current work is aimed at understanding how WNK1 regulates adhesion and migration at the molecular level and at identifying further novel pathways using CRISPR/Cas9 based screens. Furthermore, we are also investigating how the WNK1 pathway acting in B or in T cells impacts on immune responses.