Teriflunomide Inhibits Human FOXP3⁺ Regulatory T Cell Function by Interference With Mitochondrial Respiration

Area of Science:

• Immunology
• Cellular Metabolism
• Pharmacology

Background:

• Regulatory T cells (Tregs) rely on fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) for stability and function.
• Mitochondrial respiration, particularly electron transport chain complex-III, is vital for Treg suppressive activity.
• Dysfunctional Tregs in autoimmune diseases like multiple sclerosis exhibit impaired mitochondrial respiration and a T helper 1 (Th1) phenotype.

Purpose of the Study:

• To investigate the impact of teriflunomide on the immunometabolism and function of human Tregs.
• To assess how teriflunomide affects Treg mitochondrial respiration and phenotype.

Main Methods:

• Human Tregs were treated with teriflunomide.
• Mitochondrial function, including respiration and complex-III activity, was assessed.
• Treg phenotype and suppressive activity were evaluated.

Main Results:

• Teriflunomide significantly impaired mitochondrial function in human Tregs.
• The drug induced a Th1-like phenotype in Tregs.
• Teriflunomide treatment led to defective Treg suppressive activity.

Conclusions:

• Teriflunomide negatively impacts human Treg mitochondrial function and stability.
• The drug may promote a pro-inflammatory T cell profile by affecting Treg function.
• Further research is needed to understand teriflunomide's distinct effects on immune cell subsets.