Protective role of mucosa-associated invariant T cells in sepsis-related liver injury

Background and objective: Sepsis is a life-threatening condition characterized by increasing global incidence, fundamentally driven by immune dysregulation. The liver, crucial for pathogen clearance and inflammatory modulation during sepsis, frequently exhibits functional impairment. Mucosal-associated invariant T (MAIT) cells bridge innate and adaptive immunity and are integral to antimicrobial defense. Their specific role in sepsis-related liver injury (SRLI) remains unclear. This study aims to elucidate MAIT cell alterations and function in SRLI using clinical cohorts and murine models. Methods: experiments assessed effects of bilirubin and cytokines on MAIT cells. A murine SRLI model was established via intraperitoneal lipopolysaccharide (LPS) injection. Liver injury severity, inflammatory cytokines, and histopathology were compared between wild-type and MAIT cell-deficient mice. Results: assays indicated that upon stimulation, these MAIT cells preferentially produced IL-17A, TNF-α, and granzyme B, suggesting a bias toward Th17-like differentiation. Elevated concentrations of bilirubin exacerbated both the activation and exhaustion of MAIT cells through a TCR-dependent mechanism. In the septic murine model, MAIT cells deficiency led to more severe liver injury, and higher serum levels of transaminases, bilirubin, and pro-inflammatory cytokines compared to wild-type. Conclusion: In the context of SRLI, peripheral blood MAIT cells exhibit a diminished frequency, functional impairment, and a phenotypic shift toward a Th17-like profile. Among these, bilirubin plays a key role. Ultimately, MAIT cells exert a protective role in sepsis-induced liver injury by suppressing excessive inflammatory responses.