Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Janjetovic, M.
Evaluating the effect of extracellular succinate on murine CD4+ T cell polarization.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2023. pp.69.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Angiari Stefano
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- Abstract:
- The tricarboxylic acid cycle intermediate succinate accumulates in peripheral tissues during inflammation, where its receptor GPR91 (SUCNR1) enables both local tissue cells and infiltrating immune cells to detect its presence. In particular, high concentrations of succinate have been detected in the cancer microenvironment, where succinate can promote tumor growth and metastasis by influencing tumor and immune cell functionality. However, the effect of succinate on T cells is still not well understood. Our group´s preliminary results suggested that human CD4+ T cells express GPR91 on the cell surface and that their cytokine production may be influenced by extracellular succinate. The aim of this project was to investigate whether succinate may also impact murine CD4+ cell functionality. We first confirmed that murine CD4+ T cells express GPR91 on their surface. We also show that GPR91 expression is modulated by T cell activation, and various subsets of T helper (Th) cells may be able to sense extracellular succinate. In our in vitro experiments, succinate had no influence on the overall polarization of different Th cell subsets (Th1, Th2, Th17, regulatory T cells). However, we found that succinate significantly decreased IL-17A production by Th17 cells. In conclusion, the data we obtained confirm our hypothesis that T cells can sense extracellular succinate, which may influence their functionality via its receptor GPR91. This thesis highlighted GPR91 and succinate-GPR91 signaling axis as a potential target to modulate T cell-mediated inflammation.