(Vienna, 27 March 2024) A research team led by Loïc Dupré (Department of Dermatology, MedUni Vienna) has conducted experiments to identify a coordinated molecular axis that governs the functionality of T cells. The study reveals how the availability of cellular energy controls the remodelling of the actin cytoskeleton, a central cellular activity that determines the ability of T cells to migrate and establish dynamic contacts. These findings thus help to understand what makes T cells fit for their fight against pathogens and provide a possible new starting point for the development of therapies against those diseases in which the immune system is involved. The study was recently published in the scientific journal "Cell Reports".
The immune surveillance function of cytotoxic CD8+ T cells is highly dependent on their ability to migrate and scan tissue. It also depends on their ability to eliminate target cells (infected cells, tumour cells) via close contacts, so-called immunological synapses. Both migration and synapse formation are driven by intensive remodelling of the actin cytoskeleton.
Although actin remodelling has long been regarded as an energy reservoir for cells, it had not previously been investigated how the energy status of T cells could influence their actin remodelling activity and thus their ability to find and eliminate target cells," reports Loïc Dupré from the Department of Dermatology. The current study showed that energy generated by glycolysis is important for the movement and function of T cells. The study, based on samples from patients with a rare genetic defect, revealed that a protein called ARP2/3 plays a crucial role in remodelling the cell structure, i.e. the actin cytoskeleton that maintains the cell shape. If this protein does not function properly, the CD8+ T cells have difficulty moving and carrying out their cytotoxic (killing) function.
"With these findings, we have made significant progress in understanding what governs the cytotoxic activity of T cells and created the basis for research into new possibilities for T-cell centered immunotherapies," emphasises Loïc Dupré. This research work is the result of close collaboration between several research groups at MedUni Vienna's Department of Dermatology (Matthias Farlik, Wolfgang P Weninger, Loïc Dupré), the CCRI (Kaan Boztug) and the University of Vienna (Jörg Menche), as well as the Inserm in Toulouse (France), where Loïc Dupré holds a dual affiliation.
Publication: Cell Reports
Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8+ T cells
Anton Kamnev, Tanvi Mehta, Matthias Wielscher, Beatriz Chaves, Claire Lacouture, Anna-Katharina Mautner, Lisa E Shaw, Michael Caldera, Jörg Menche, Wolfgang P Weninger , Matthias Farlik, Kaan Boztug, Loïc Dupré
DOI: 10.1016/j.celrep.2024.113853