WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses
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 t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56778-x |
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| author | Joshua Biggs O’May Lesley Vanes Leonard L. de Boer David A. Lewis Harald Hartweger Simone Kunzelmann Darryl Hayward Miriam Llorian Robert Köchl Victor L. J. Tybulewicz |
| author_facet | Joshua Biggs O’May Lesley Vanes Leonard L. de Boer David A. Lewis Harald Hartweger Simone Kunzelmann Darryl Hayward Miriam Llorian Robert Köchl Victor L. J. Tybulewicz |
| author_sort | Joshua Biggs O’May |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bfa737ae10e149d88975b788b64fea97 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bfa737ae10e149d88975b788b64fea972025-08-20T01:57:45ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56778-xWNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responsesJoshua Biggs O’May0Lesley Vanes1Leonard L. de Boer2David A. Lewis3Harald Hartweger4Simone Kunzelmann5Darryl Hayward6Miriam Llorian7Robert Köchl8Victor L. J. Tybulewicz9The Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteThe Francis Crick InstituteAbstract 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.https://doi.org/10.1038/s41467-025-56778-x |
| spellingShingle | Joshua Biggs O’May Lesley Vanes Leonard L. de Boer David A. Lewis Harald Hartweger Simone Kunzelmann Darryl Hayward Miriam Llorian Robert Köchl Victor L. J. Tybulewicz WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses Nature Communications |
| title | WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses |
| title_full | WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses |
| title_fullStr | WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses |
| title_full_unstemmed | WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses |
| title_short | WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses |
| title_sort | wnk1 dependent water influx is required for cd4 t cell activation and t cell dependent antibody responses |
| url | https://doi.org/10.1038/s41467-025-56778-x |
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