Researchers from the National Institute of Scientific Research (INRS) and McGill University highlighted the key role of the IRF-5 transcription factor in preserving the energy of CD8+cells, essential for immune defense.
A central actor against the exhaustion of T cells
CD8+T cells, real pillars of the immune response, see their effectiveness decline in the face of persistent threats such as chronic infections or certain cancers. This state, called “exhaustion”, weakens the immune response of the body. Professor Simona Stäger, an immunology specialist in infectious diseases at INRS, and her team discovered that the IRF-5 transcription factor plays a crucial role in resistance to this weakening. It would act as a regulator of cellular metabolism, allowing T cells to keep their vitality.
An energy metabolism at stake
Normally, in response to an infection, T cells modify their energy production to respond quickly to the threat. But in chronic situations, this capacity collapses: the mitochondria weaken, the production of cytokines slows down and the immune functions decline. The study conducted with the LCMV Clone 13 virus, a model of chronic infection in mice, demonstrates that the absence of IRF-5 worsens this phenomenon. Private cells of this factor have high oxidative stress, mismanagement of lipids and a reduction in oxidative phosphorylation, which harms their effectiveness.
A promising track for therapeutic research
These results offer a better understanding of the mechanisms that govern the vitality of T cells in extended immune stress contexts. For Linh Thuy Mai, the first author of the study and postdoctoral researcher at the Albert Einstein College of Medicine, this discovery opens the way to new clinical approaches. The idea would be to modulate the metabolism of T cells to prolong their effectiveness and strengthen immune responses in cases of chronic infections or cancers, where T cells are exhausted prematurely.
A concrete example of the importance of basic research
This study illustrates the central role of basic research in the identification of biological targets likely to change medical treatments. By deeply exploring cellular mechanisms, Quebec researchers show that modulation of a single factor-IRF-5-can have major effects on the performance of the immune system. These works also help to position the INRS and its partners as key players in the biomedical research ecosystem in Quebec.
Multidisciplinary scientific collaboration
The project was carried out at the Armand-Frappier Health Biotechnology of INRS Center, in collaboration with researchers from McGill University. It is part of the dynamics of infectiopôle and benefits from the support of Canada’s health research institutes, the Armand-Frappier Foundation and the Quebec Research Fund. The study published under the title Transcription Factor IRF-5 Regulates Lipid Metabolism and Mitochondrial Function in Murine CD8+ T-Cells During Viral Infection is co-signed by a dozen researchers. Their collective contribution testifies to the importance of interdisciplinary work to better understand and fight major diseases.
Source: National Institute of Scientific Research (INRS)
Publication Index Health: 2025-07-25
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