{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:19:09Z","timestamp":1788297549339,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Regulatory FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid \u03b2\u2010oxidation (FAO) and oxidative phosphorylation (OXPHOS). Several studies have indicated that Treg mitochondrial fitness is crucial for maintaining their stability and suppressive activity with an emphasis on complex\u2010III of the electron transport chain (ETC). Dysfunctional Tregs isolated from patients with autoimmunity like multiple sclerosis (MS) show diminished mitochondrial respiration and the induction of a T helper (Th)1\u2010like phenotype, characterized by increased production of interferon (IFN)\u2010\u03b3. Teriflunomide reduces the proliferation of activated T and B lymphocytes by inhibition of de novo pyrimidine synthesis, providing therapy for patients with autoimmune diseases. Recent data demonstrated that teriflunomide further inhibited complex\u2010III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex\u2010III activity for Tregs, we therefore thought to investigate with this study the effects of teriflunomide on immunometabolism and function in human Tregs. Interestingly, teriflunomide impaired the mitochondrial function of human Tregs and further induced a Th1\u2010like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro\u2010 versus anti\u2010inflammatory T cell subsets, indicating the need for further detailed evaluation.\n                  <\/jats:p>","DOI":"10.1002\/eji.202451260","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T06:42:57Z","timestamp":1753080177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Teriflunomide Inhibits Human FOXP3\n                    <sup>+<\/sup>\n                    Regulatory T Cell Function by Interference With Mitochondrial Respiration"],"prefix":"10.1002","volume":"55","author":[{"given":"Aleksandra","family":"Dyczko","sequence":"first","affiliation":[{"name":"Laboratory of Translational Immunomodulation VIB Center for Inflammation Research (IRC) Hasselt University  Diepenbeek Belgium"},{"name":"Department of Immunology and Infection Biomedical Research Institute (BIOMED) Hasselt University  Diepenbeek Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz F.","family":"C\u00f4rte\u2010Real","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunomodulation VIB Center for Inflammation Research (IRC) Hasselt University  Diepenbeek Belgium"},{"name":"Department of Immunology and Infection Biomedical Research Institute (BIOMED) Hasselt University  Diepenbeek Belgium"},{"name":"Department of Molecular Cell Biology and Immunology Amsterdam Institute for Infection and Immunity Cancer Centre Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Hamad","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunomodulation VIB Center for Inflammation Research (IRC) Hasselt University  Diepenbeek Belgium"},{"name":"Department of Immunology and Infection Biomedical Research Institute (BIOMED) Hasselt University  Diepenbeek Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf A.","family":"Linker","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kleinewietfeld","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunomodulation VIB Center for Inflammation Research (IRC) Hasselt University  Diepenbeek Belgium"},{"name":"Department of Immunology and Infection Biomedical Research Institute (BIOMED) Hasselt University  Diepenbeek Belgium"},{"name":"University MS Center (UMSC) UHasselt  Diepenbeek 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