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Dietary Restriction Maintains Mitochondrial Homeostasis of CD4+ T Cells Through Purine Metabolism and Reduces Post-Stroke Immunosuppression

Laufzeit: 01.01.2021 - 31.12.2023

Kurzfassung


The major impact of ischemic stroke on the immune system often leads to immunosuppression associated with fatal infection. Currently, there is no effective intervention. Our research group in Shanghai and Dr. Sparwasser's group in Germany have been collaborating for many years in a study of cellular metabolic modulation of CD4+ T cells, which play a critical role in combating infectious diseases. Through this collaborative project, we found that CD4+ T cells exhibit significant phenotypic...The major impact of ischemic stroke on the immune system often leads to immunosuppression associated with fatal infection. Currently, there is no effective intervention. Our research group in Shanghai and Dr. Sparwasser's group in Germany have been collaborating for many years in a study of cellular metabolic modulation of CD4+ T cells, which play a critical role in combating infectious diseases. Through this collaborative project, we found that CD4+ T cells exhibit significant phenotypic changes after stroke associated with marked alterations in intracellular metabolism, whereas dietary restriction (DR) can reverse the above changes. In this project, our preliminary experiments with combined analysis of the metabolome and transcriptome showed that DR increased guanosine monophosphate reductase (Gmpr) expression in CD4+ T cells and decreased purine metabolism. Purine metabolites are thought to induce mitochondrial fission and may destroy mitochondrial DNA homeostasis. Therefore, it is hypothesized that DR can improve the immune homeostasis of CD4+ T cells and reduce the incidence of infectious complications by increasing Gmpr and reducing purine metabolism, which contributes to the maintenance of mitochondrial DNA homeostasis in CD4+ T cells. State-of-the-art experimental techniques, such as combined analysis of the metabolome and transcriptome, flow cytometry, and Crispr-Cas9 genetic editing of primary T cells, are being used to investigate the above hypothesis to identify novel mechanisms of immunosuppression after stroke and to explore new therapeutic targets.» weiterlesen» einklappen

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