2023-08-31 16:15:09
Scientists from St. Anna Children’s Cancer Research and Marmara University have researched the basics of immune metabolism using the example of a congenital immune defect.
Vienna (OTS) – Immune metabolism is a central topic of research. Which nutrients are absorbed and how they are processed is not only determined by the cell, but also by its function. T cells need to be able to process glucose (sugar) to do their job, the vital human response to pathogens or cancer cells. If this metabolism is disturbed, then they can only perform insufficiently. Scientists under the direction of St. Anna Children’s Cancer Research and Marmara University Istanbul have now been able to show for the first time that a congenital mutation in three affected patients of the transcription factor NFATC1, which is important for the activation of T cells, causes a previously unknown immune defect: the Patients suffer from recurring infections and inflammation.
The first author of the now in the journal Blood published study, DDr. Sevgi Köstel Bal, a postdoc at St. Anna Children’s Cancer Research in the group of Dr. Kaan Boztug speaks of a rare disease that can be a model for the immune metabolism and conscious interventions in it. You’ve seen very clearly that a T cell needs energy, she says. However, if glucose cannot be processed, then the human body becomes ill. You can think of it in terms of a car that doesn’t drive optimally because the fuel can’t be processed properly. By administering an anti-diabetes medication that has been known for decades, such as metformin or rosiglitazone, “the immune cells increasingly resorted to fat as an energy source,” says Sevgi Köstel Bal. “So we retrained the immune cells.”
The cells trained for fat
The drugs are usually given in type 2 diabetes to facilitate the absorption of insulin to convert carbohydrates into energy. “We believe that there is huge potential in the field of immune metabolism for the treatment of such defects as well. In our study, we were not only able to discover a new immune defect, but above all to show that the function of the patient’s immune cells could be improved again – by normalizing the metabolism in the immune cells, although it is a congenital immune defect. “, says Kaan Boztug, senior author of the study, scientific director at St. Anna Children’s Cancer Research, professor at the Medical University of Vienna and adjunct principal investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (ÖAW).
Whether the mutation of NFATC1, like many other congenital gene defects of the immune system, increases the risk of cancer in humans has yet to be finally clarified, says Boztug. The question of whether the defect can cause an autoimmune reaction, i.e. the destruction of the body’s own cells by the human body, has not yet been answered. In any case, this reaction was demonstrated in the mouse model. Research is therefore still needed to understand the NFATC1 gene defect and its effects in more detail. This is also the view shared by Safa Baris of Marmara University, co-latest author of the study, Professor of Pediatric Allergy and Immunology. He led patient recruitment.
In the future, the results of Bloodstudy will in any case lead to personalized therapies that specifically target the molecular causes of immune diseases – with the help of immune modulation. Deliberately influencing the immune system with drugs to fine-tune it without causing an overreaction or a suppression would be a significant advance in the treatment of rare diseases like this, says Boztug.
The attached photo shows the study authors Kaan Boztug and Sevgi Köstel Bal. Credit: Luke Lach
Questions & contact:
Peter Illetschko
Science Communcation Manager
St. Anna Children’s Cancer Research GmbH
(St. Anna Children’s Cancer Research Institute)
Zimmermannplatz 10, 1090 Vienna, Austria
T +43 1 40470-0 F +43 1 40470-7150
M +43 664 547 72 95
peter.illetschko@ccri.at www.ccri.at
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