Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Mayer, AL.
Metabolic regulation of TH9 cell development.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2023. pp.89.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Angiari Stefano
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- Abstract:
- TH9 cells, a relatively novel subset of CD4+ T cells, are polarized from naïve CD4+ T cells by TGF-β and IL-4, and produce IL-9 as their characteristic pleiotropic cytokine. In recent years, there has been growing recognition of the significance of TH9 cells and their associated functional factors in various clinical conditions, including inflammatory and autoimmune diseases, tumors, and related pathologies. In this project, our aim was to investigate potential metabolic regulators and associated signaling cascades of TH9 cells by examining the impact of various metabolites on them. Recently, it has been recognized that the intermediate succinate, which is generated in the TCA cycle, plays a significant role in inflammatory responses. Succinate may act as a type of “metabolic signal" released by activated or stressed tissue and immune cells. First, we confirmed that murine and human TH9 cells express GPR91 on the surface and TH9 cells may be able to sense extracellular succinate. When we analyzed the effect of 1 mM and 5 mM succinate on human TH9 polarization, we found no effect. However, we found that 5 mM succinate increased the production of interleukin-9 in vitro in murine TH9 cells. Given the physiological importance of IL-9 in antitumor immunity, our results showed that a high concentration, as also present in tumor microenvironment, can elicit a TH9-dependent antitumor immune response in mice, but not in humans.