T cell migration requires ion and water influx to regulate actin polymerization.

Autor: de Boer LL; The Francis Crick Institute, London, NW1 1AT, UK.; Department of Immunology and Inflammation, Imperial College London, London, W12 0NN, UK.; Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, 171 65, Stockholm, Sweden., Vanes L; The Francis Crick Institute, London, NW1 1AT, UK., Melgrati S; The Francis Crick Institute, London, NW1 1AT, UK.; Department of Immunology and Inflammation, Imperial College London, London, W12 0NN, UK.; Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Biggs O'May J; The Francis Crick Institute, London, NW1 1AT, UK., Hayward D; The Francis Crick Institute, London, NW1 1AT, UK.; GSK, Stevenage, SG1 2NY, UK., Driscoll PC; The Francis Crick Institute, London, NW1 1AT, UK., Day J; Department of Earth Sciences, University of Cambridge, Cambridge, CB2 3EQ, UK., Griffiths A; London Metallomics Facility, Research Management & Innovation Directorate, King's College London, London, SE1 1UL, UK., Magueta R; London Metallomics Facility, Research Management & Innovation Directorate, King's College London, London, SE1 1UL, UK., Morrell A; London Metallomics Facility, Research Management & Innovation Directorate, King's College London, London, SE1 1UL, UK., MacRae JI; The Francis Crick Institute, London, NW1 1AT, UK., Köchl R; The Francis Crick Institute, London, NW1 1AT, UK.; Kings College London, London, SE1 9RT, UK., Tybulewicz VLJ; The Francis Crick Institute, London, NW1 1AT, UK. Victor.T@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 06; Vol. 14 (1), pp. 7844. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1038/s41467-023-43423-8
Abstrakt: Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4 + T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.
(© 2023. The Author(s).)
Databáze: MEDLINE
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