Antioxidant interventions reduced cytokine-induced pyroptosis of peripheral MAIT cells in patients with HBV-related cirrhosis.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are diminished in various liver diseases, but the underlying mechanism remains unclear. This study aimed to investigate the characteristics and underlying mechanisms of MAIT cell depletion in HBV-related cirrhosis. METHODS: Peripheral blood samples were collected from 20 healthy controls and 40 patients with HBV-related cirrhosis, divided into compensated (20) and decompensated (20) liver cirrhosis groups. Flow cytometry, single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence, and ELISA were used to assess MAIT cell characteristics. RESULTS: In patients with HBV-related cirrhosis, MAIT cells were significantly reduced and hyperactivated. The levels of pyroptosis and oxidative stress were elevated, particularly in those with decompensated liver cirrhosis (DLC). As disease severity increased, both pyroptosis and oxidative stress in MAIT cells rose, negatively correlating with MAIT cell frequency. Additionally, MAIT cells from patients with compensated liver cirrhosis (CLC) and DLC had lower levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granzyme B (GZMB), and CD107a, but higher IL-17A levels. Blocking IL-12 and IL-18 pathways reduced MAIT cell activation and pyroptosis, while antioxidants effectively decreased pyroptosis in vitro. CONCLUSIONS: Pyroptosis contributes to the decline of MAIT cells in HBV-related cirrhosis, while antioxidants can reduce this process.