Regulating T Cell Volume and Proliferation via Water Influx

Researchers at the Francis Crick Institute have shown that the entry of water into immune cells, such as T cells, is a key requirement for their activation and proliferation when responding to threats.

T cells play a crucial role in defending against infections and other threats to the body. In their resting state, these small cells continuously circulate in the bloodstream. However, when they encounter antigens—foreign substances from viruses or bacteria—they become activated, grow in size, and rapidly divide. This process generates a population of T cells specifically designed to recognize and eliminate the invading antigen.

The Crick team’s findings, published in Nature Communications, highlight the role of a protein called WNK1 in this process. WNK1 facilitates water entry through channels on the T cell surface and is essential for initiating activation. This builds on previous research from the same lab in 2023, which established WNK1’s importance in T cell migration.

In the study, researchers compared the responses of mouse T cells—with and without WNK1—when stimulated using a lab technique that mimics an infection. They found that mice lacking WNK1 in their T cells had significantly fewer responding cells and failed to generate antibodies, indicating an impaired immune response.

Further analysis revealed that WNK1 activity triggers the movement of ions—sodium, potassium, and chloride—into the cell, followed by water entering through membrane channels called aquaporins via osmosis. This influx of water was crucial for T cells to progress through the cell cycle and divide. Without WNK1, T cells moved through the cycle more slowly, leading to a reduced number of newly generated cells.

To confirm the role of water in this process, researchers exposed WNK1-deficient T cells to a low-salt solution, prompting a rapid influx of water. This restored their ability to divide normally, demonstrating that water entry is a necessary condition for cell division.

Because WNK1 is present in most cell types, the study suggests that water influx could be a fundamental mechanism in cell replication. If cancer cells exploit this pathway to fuel their rapid growth, these findings could have implications for cancer research and treatment strategies.

Building a Clearer Picture of T Cell Activation

“Our research shows just how crucial WNK1 is for an effective immune response. Combining this with our previous findings on WNK1’s role in T cell migration, we are beginning to see a more complete picture of how immune cells quickly activate, move to where they’re needed, and respond effectively,” said Joshua Biggs O’May, former PhD student and first author of the study.

“The role of water in cell biology is often overlooked, thought of merely as a passive solvent,” added Victor Tybulewicz, Group Leader of the Immune Cell Biology and Down Syndrome Laboratories at the Francis Crick Institute. “But our work shows that water actively transmits signals that control T cell migration and division. We are now investigating how universal this process is, as it may also play a role in the rapid division of cancer cells and other fundamental cellular functions.”

This research opens new avenues for exploring how water dynamics influence immune responses and disease progression. Further studies could help determine whether targeting this mechanism might lead to new therapeutic approaches for immune disorders or cancer.