WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses

Joshua Biggs O’May, Lesley Vanes, Leonard L. Boer, David A. Lewis, Harald Hartweger, Simone Kunzelmann, Darryl Hayward, Miriam Llorian, Robert Köchl and Victor L. J. Tybulewicz ()
Additional contact information
Joshua Biggs O’May: The Francis Crick Institute
Lesley Vanes: The Francis Crick Institute
Leonard L. Boer: The Francis Crick Institute
David A. Lewis: The Francis Crick Institute
Harald Hartweger: The Francis Crick Institute
Simone Kunzelmann: The Francis Crick Institute
Darryl Hayward: The Francis Crick Institute
Miriam Llorian: The Francis Crick Institute
Robert Köchl: The Francis Crick Institute
Victor L. J. Tybulewicz: The Francis Crick Institute

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Signaling from the T cell antigen receptor (TCR) on CD4+ T cells plays a critical role in adaptive immune responses by inducing T cell activation, proliferation, and differentiation. Here we demonstrate that WNK1, a kinase implicated in osmoregulation in the kidney, is required in T cells to support T-dependent antibody responses. We show that the canonical WNK1-OXSR1-STK39 kinase signaling pathway is required for TCR signaling in CD4+ T cells, their subsequent entry into the cell cycle, and suppression of the ATR-mediated G2/M cell cycle checkpoint. We show that the WNK1 pathway regulates ion influx leading to water influx, potentially through AQP3, and that water influx is required for TCR-induced signaling and cell cycle entry. Thus, TCR signaling via WNK1, OXSR1, STK39 and AQP3 leads to water entry that is essential for CD4+ T cell proliferation and hence T cell-dependent antibody responses.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56778-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56778-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56778-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().