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<p>Signaling from the T cell antigen receptor (TCR) on CD4<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cell proliferation and hence T cell-dependent antibody responses.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月21日

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  • 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

摘要

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.