Apigenin ameliorates lupus nephritis by inhibiting SAT3 signaling in CD8+ T cells

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ and tissue involvement, with lupus nephritis (LN) being one of its most severe complications. Dietary flavonoids, as for their anti-inflammatory and antioxidant properties, have shown therapeutic potential under various inflammatory conditions. Apigenin (AP) is one of the most studied phenolics and is found in many fruits, vegetables and herbs. This study aimed to investigate the therapeutic effects and underlying mechanisms of apigenin on LN. We evaluated the effects of apigenin on MRL/lpr mice, a well-established model for spontaneous LN. Apigenin treatment improved peripheral blood profiles, reduced serum inflammatory cytokines (IL-6, IFN-γ, IL-17, TGF-β), lowered levels of autoantibodies (ANA, anti-dsDNA) and alleviated renal damage caused by autoantibodies and inflammatory cell infiltration. The results of immunohistochemistry and transcriptome analysis showed that AP could inhibit the infiltration of CD8⁺ cells in renal tissues. Single-cell sequencing public data from LN patients identified cytotoxic T lymphocytes (CTLs) as the primary CD8⁺ T cell subtype in the kidneys, with their differentiation regulated by STAT3. In this study, cell experiments demonstrated that AP can induce apoptosis in CD8⁺ T cells and reduce their recruitment of macrophages by inhibiting the STAT3/IL-17 signaling pathway. These findings highlight that a diet rich in dietary flavonoids, particularly apigenin, can offer therapeutic benefits for patients with SLE.