Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8⁺ T-cells during viral infection

Mai, Linh Thuy; Swaminathan, Sharada; Nguyen, Trieu Hai; Collette, Étienne; Charpentier, Tania; Carmona-Pérez, Liseth; Loucif, Hamza; Lamarre, Alain ORCID: https://orcid.org/0000-0002-7913-871X; Heinonen, Krista M. ORCID: https://orcid.org/0000-0002-2410-4432; Langlais, David; Fritz, Jorg et Stäger, Simona ORCID: https://orcid.org/0000-0001-5508-9565 (2025). Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8⁺ T-cells during viral infection Embo Journal , vol. ahead of p . pp. 1-21. DOI: 10.1038/s44318-025-00485-2. (Sous Presse)

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Résumé

Exhaustion of CD8+ T-cells leads to their reduced immune functionality and is controlled by numerous transcription factors. Here we show that the transcription factor IRF-5 helps to limit functional exhaustion of murine CD8+ T-cells during the chronic stage of LCMV (CL13) viral infection. Our results suggest that T-cell inhibitory receptors and transcription factor TOX, which are implicated in dampening T-cell activation and promoting exhaustion, are upregulated in infected IRF-5-deficient CD8+ T-cells. In addition, these cells display a reduced capacity to produce cytokines and lower survival rates than wild-type cells. Our findings indicate that these effects are mediated by defective lipid metabolism, increased lipid peroxidation, enhanced mitochondrial ROS production, and reduced levels of oxidative phosphorylation in the absence of IRF-5. These results identify IRF-5 as an important regulator of lipid metabolism and mitochondrial function that protects CD8+ T-cells from functional exhaustion during the chronic stage of viral infection.

Type de document:	Article
Informations complémentaires:	supported by scholarships from the Fondation Armand-Frappier and the Fonds de Recherche du Québec – Santé (FRQS). We thank the Canadian Institutes of Health Research (PJT-190001 to SS.; PJT-148614 to KMH; PJT-175173 to JHF; PJT -168959 to DL) for financial suppor
Mots-clés libres:	CD8 T Cells; Cell Exhaustion; IRF-5; Lipid Metabolism; Mitochondria
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	07 juill. 2025 19:09
Dernière modification:	07 juill. 2025 19:09
URI:	https://espace.inrs.ca/id/eprint/16541

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