Coronin 1 Signaling Pathway Suppresses T Cell Death

Researchers at the University of Basel have uncovered a previously unknown signaling pathway essential for T cell viability. In Science Signaling they report that this signaling pathway, regulated by the protein coronin 1, is responsible for suppressing T cell death.

To hunt down this coronin 1-dependent pathway, the researchers established a procedure to collect highly pure T cells and subsequently analyzed the whole set of RNA molecules in normal and coronin 1-deficient T cells. “Somewhat unexpectedly, in-depth bioinformatics analysis of the many gigabytes of data did not reveal any difference between these two groups of T cells. That’s when the Covid-19-induced lockdown came in,” says Jean Pieters, the lead author. “So, I decided to use the home-office time to sift through the many tables and lists of genes to see if there were any correlations with known signaling pathways whose deregulation could explain the disappearance of T cells upon coronin 1 depletion.”

Strikingly, there was a positive match linking coronin 1-dependent T cell survival to a pathway involving the modification of the plasma membrane composition by the lipid kinase PI3Kdelta. The researchers were able to put together the pieces of the puzzle, leading to their realization that coronin 1 maintains PI3Kdelta activity and, in this way, suppresses T cell death.

“It will now be exciting to follow up on these findings, not only to understand the role of other members of the coronin protein family in cell survival but also how cell populations, such as circulating T cells in the blood, are being maintained long-term,” says Pieters. Finally, given the importance of T cells for regulating processes as diverse as viral and microbial pathogen resistance, tumorigenicity, and autoimmunity, this work may contribute to better control of both appropriate as well as undesirable T cell activities.