Ferroptosis Role in the Pathophysiology of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting various organs. Regulatory T cells (Treg) and platelets play a crucial role in the pathogenesis of SLE by regulating immunity and promoting inflammation. Ferroptosis, an iron-regulated cell death process, is emerging as a key player in many diseases, including SLE.

The project, FERROLUP, aims to understand the role of ferroptosis in SLE and to explore the therapeutic potential of selenium compounds to modulate this process. Recent work has identified down-regulation of glutathione peroxidase 4 (GPx4) by immune complexes and interferon-alpha in neutrophils, leading to ferroptosis and worsening of SLE. In addition, data suggest the involvement of ferroptosis in lupus nephritis.

The Bordeaux team has developed selenium compounds, GPx4 mimics, capable of inhibiting ferroptosis in lupus neutrophils. These compounds have shown promising efficacy in mouse models and preliminary human studies in another inflammatory disease. The FERROLUP project aims to characterize the level of lipid peroxidation and GPx4 expression in SLE patients, and to test the impact of selenium compounds on the inhibition of ferroptosis induced by P-selectin, a molecule involved in Treg dysfunction.

• Measurement of lipid peroxidation in regulatory T lymphocytes population in lupus subjects and controls. [Срок оценки: At baseline (Day 0)]
• Measurement of lipid peroxidation in other immune cells (T and B lymphocyte populations) in lupus subjects and controls [Срок оценки: At baseline (Day 0)]
• GPX4 expression in lupus subjects and controls. [Срок оценки: At baseline (Day 0)]
• Correlation between ferroptosis markers and the level of activity in B lymphocyte populations [Срок оценки: At baseline (Day 0)]
• In-vitro effect of BXT on different T lymphocytes population in the presence of P-selectin in sera of lupus subjects and controls [Срок оценки: At baseline (Day 0)]