In fighting chronic infections or certain cancers, CD8+ T cells-the immune system’s frontline soldiers-eventually become exhausted. They lose effectiveness and respond less efficiently to threats. This weakening is a major therapeutic challenge, as it limits the body’s ability to fight chronic infections.<\/p>\n
However, the team of Professor Simona St\u00e4ger at Institut national de la recherche scientifique (INRS), in collaboration with colleagues from INRS and McGill University, has identified a key game changer: IRF-5. This transcription factor appears to preserve the energy and vitality of CD8+ T cells<\/a> by acting directly on their metabolism.<\/p>\n These findings, recently published in The EMBO Journal, highlight the importance of fundamental research in understanding the immune system and developing innovative therapeutic approaches.<\/p>\n A key ally against T cell exhaustion<\/p>\n T cell exhaustion is caused by several factors, including an imbalance in internal cell functioning. Normally, T cells shift their energy production to respond quickly to infection. But when they are stimulated for too long-as during chronic infections-their metabolism becomes depleted. They produce fewer cytokines (chemical messengers essential to the immune response), their mitochondria (the cell’s energy centres) function less efficiently, and they ultimately lose their effectiveness.<\/p>\n In this study, the team used the LCMV Clone 13 virus, a model of chronic infection, to explore the role of IRF-5 in CD8+ T cells. While the role of IRF-5 in other cell types is well known, its function in these immune cells had not been explored until now.<\/p>\n
<\/p>\n Our results show that IRF-5 acts as a guardian of T cell metabolism and mitochondrial function. It helps T cells maintain their energy and ability to fight, even under prolonged stress.”<\/p>\n
Simona St\u00e4ger, INRS professor and senior author of the study, expert in immunology of infectious diseases, and Vice-director of Infectiopole<\/p>\n
<\/p>\n The researchers found that the absence of IRF-5 worsens exhaustion. CD8+ T cells lacking IRF-5 showed disrupted lipid metabolism, increased mitochondrial oxidative stress, and reduced oxidative phosphorylation-all factors that impair their function.<\/p>\n A promising step toward better understanding immunity<\/p>\n This discovery opens the door to new strategies for boosting immunity to chronic infections or cancers, where T cell exhaustion is also observed.<\/p>\n “I hope our work will help us better understand how to modulate cellular metabolism to support and enhance immune responses during chronic infections or cancer. IRF-5 transcription factor could play a key role in this approach.”<\/p>\n -Linh Thuy Mai, lead author of the study, former PhD student in virology and immunology from INRS, currently a postdoctoral fellow at Albert Einstein College of Medicine, United States.<\/p>\n Professor St\u00e4ger’s laboratory is based at the INRS Armand-Frappier Sant\u00e9 Biotechnologie Research Centre, the sole North American member of the Pasteur Network\u00a0.<\/p>\n Source:<\/p>\n Institut national de la recherche scientifique – INRS<\/a><\/p>\n Journal reference:<\/p>\n
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