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 triggers the adaptive immune response by inducing T cell activation, proliferation, and differentiation. However, TCR signaling pathways are incompletely understood. Unexpectedly, we demonstrate that WNK1, a kinase previously implicated in osmoregulation in the kidney, is required for T-dependent antibody responses. We show that WNK1-OXSR1-STK39-dependent water influx through AQP3 is required for TCR signaling in CD4+ T cells and for entry into cell cycle. Additionally, by preventing ATR activation this signaling pathway is required for T cells to progress through the G2 phase of the cell cycle. 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.

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

“…More broadly, in a parallel study we have been able to show that T cell antigen receptor (TCR) stimulation of CD4 + T cells results in the activation of the WNK1 pathway and that the resulting ion and water influx are required for TCR-induced cell proliferation 40 . These results suggest that multiple signaling receptors may co-opt the WNK1 pathway to regulate ion and water movement, which are required for migration, proliferation and perhaps other fundamental physiological processes.…”