T cells defend against infections and other threats to the body. Small T cells are constantly moving around in a resting state, but in the presence of antigens – foreign material from viruses and bacteria – T cells switch on, enlarge in size and start dividing very quickly. This creates a batch of T cells able to recognise and destroy that particular antigen.

In research published this in Nature Communications, the team at the Crick found that a protein called WNK1 causes water to enter through channels on the T cell surface and is required to kick-start this process. This follows research from the lab in 2023, showing that WNK1 is necessary for T cell migration.

In the new study, the scientists compared what happened when mouse T cells, with and without WNK1, were triggered by a lab technique mimicking an infection.  

They found that in mice with WNK1-deficient T cells, the number of T cells responding to the infection was greatly reduced and the mice were unable to produce antibodies, proteins which are a hallmark of an immune response that depends on T cells.

The team also observed that WNK1 activity causes ions – sodium, potassium and chloride – to enter the cell. Water then follows by osmosis, through channels on the membrane called aquaporins.

This process was essential for the T cells to enter and commit to the cell cycle, resulting in cell division. WNK1 was important for progression around the cycle and for bypassing checkpoints which can slow down the process, as T cells without WNK1 progressed more slowly, resulting in fewer new cells.

Finally, the researchers placed T cells without WNK1 into a low-salt solution causing water to rush into the cells. Importantly, this restored their ability to divide normally, demonstrating that water influx is necessary for cell division.

WNK1 is found in most cell types, so this work suggests that water influx may be a common feature of cell replication. This could have implications for disease, for example if cancer cells are found to co-opt this pathway to their advantage.

Joshua Biggs O’May, former PhD student at the Crick and first author of the study, said: 

By removing WNK1 from T cells in mice, we’ve shown just how important it is for an effective immune response to infections. Combining this with our previous research showing that WNK1 is needed for T cell migration, we’ve started to build a fuller picture of how this critical element of the immune system is switched on quickly and allows immune cells to get to where they’re needed in the body and to respond effectively.

Victor Tybulewicz, Group Leader of the Immune Cell Biology Laboratory & Down Syndrome Laboratory at the Crick, said:

The role of water is understudied – it’s often thought of as just a passive solvent for biological molecules to function in. But our work shows that water has an active role as a messenger, transmitting signals into the T cell that control its migration and division.

We’re now looking at how universal this process is, as it could have implications for how cancer cells can divide more rapidly, or play fundamental roles in other cell types.