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Here we show that the transcription factor IRF-5 helps to limit functional exhaustion of murine CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T-cells from functional exhaustion during the chronic stage of viral infection.\n                  <\/jats:p>","DOI":"10.1038\/s44318-025-00485-2","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T08:14:10Z","timestamp":1749543250000},"page":"4280-4300","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection"],"prefix":"10.1038","volume":"44","author":[{"given":"Linh Thuy","family":"Mai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharada","family":"Swaminathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trieu Hai","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Collette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Charpentier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liseth","family":"Carmona-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza","family":"Loucif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lamarre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-4432","authenticated-orcid":false,"given":"Krista M","family":"Heinonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-0110","authenticated-orcid":false,"given":"David","family":"Langlais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg H","family":"Fritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-9565","authenticated-orcid":false,"given":"Simona","family":"St\u00e4ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"485_CR1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/cei.13573","volume":"204","author":"GJ Albers","year":"2021","unstructured":"Albers GJ, Iwasaki J, McErlean P, Ogger PP, Ghai P, Khoyratty TE, Udalova IA, Lloyd CM, Byrne AJ (2021) IRF5 regulates airway macrophage metabolic responses. 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