Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Klemen, I.
Regulation of CD8+ Tc2 cell functionality by the metabolite succinate.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2025.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Angiari Stefano
- Altmetrics:
- Abstract:
- The tricarboxylic acid cycle intermediate succinate has been reported to act beyond its conventional role in energy metabolism, showing important intra- and intercellular signaling functions. In particular, succinate can modulate inflammatory responses by regulating immune cell activation, polarization and effector functions. High succinate concentrations have been detected in several tissues during inflammation, where it can be sensed by cells via the succinate receptor G-protein coupled receptor 91 (GPR91). Notably, high levels of succinate have also been found in tumor tissues, where it controls the metastatic potential of tumor cells and limits the anti-tumor activity of infiltrating leukocytes such as macrophages. However, while the effect of succinate sensing via GPR91 have been studied in different immune cells, the impact of succinate on T cells is still unclear. Preliminary data from our laboratory indicate that succinate boosts subset-specific cytokine production by murine and human CD4+ T helper 2 (Th2) cells, and that this effect may be GPR91-dependent. This project aims to investigate the effect of extracellular succinate on murine and human CD8+ type 2 cytotoxic T cells (Tc2). We confirmed that GPR91 is expressed in murine and human CD8+ cells, and that its expression is modulated upon T cell activation. We could also show that the production of IL-4, IL-5, IL-13 and IL-10 by murine and human Tc2 cells is boosted by succinate, mirroring our previous results on Th2 cells. Overall, these new data support our hypothesis that T cell functionality may be shaped by extracellular succinate, and that succinate may preferentially induce a type 2-like immune response. We suggest that cancer cells might use these effects to escape immunosurveillance by releasing succinate into the surrounding microenvironment.