Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/46577
Title: Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration
Authors: DYCZKO, Aleksandra 
FERNANDES CORTE-REAL, Beatriz 
HAMAD, Ibrahim 
Linker, Ralf A.
KLEINEWIETFELD, Markus 
Issue Date: 2025
Publisher: WILEY
Source: European Journal of Immunology, 55 (7) (Art N° e51260)
Abstract: Regulatory FOXP3+ T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid beta-oxidation (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-III 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-like phenotype, characterized by increased production of interferon (IFN)-gamma. 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-III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex-III 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-like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro- versus anti-inflammatory T cell subsets, indicating the need for further detailed evaluation.
Notes: Kleinewietfeld, M (corresponding author), Hasselt Univ VIB, Ctr Inflammat Res IRC, Lab Translat Immunomodulat, Diepenbeek, Belgium.; Kleinewietfeld, M (corresponding author), Hasselt Univ, Biomed Res Inst BIOMED, Dept Immunol & Infect, Diepenbeek, Belgium.; Kleinewietfeld, M (corresponding author), Univ MS Ctr UMSC, UHasselt, Diepenbeek, Belgium.
markus.kleinewietfeld@uhasselt.be
Keywords: autoimmunity;regulatory T cells;immunometabolism;multiple sclerosis;teriflunomide
Document URI: http://hdl.handle.net/1942/46577
ISSN: 0014-2980
e-ISSN: 1521-4141
DOI: 10.1002/eji.202451260
ISI #: 001543503100021
Rights: 2025 Wiley-VCH GmbH
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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