Abstract
Macrophages play a critical role in the regulation of the inflammatory responses in sepsis. Methyltransferase like 7B (METTL7B) has been implicated in several pathophysiological conditions. Nevertheless, the potential engagement of METTL7B in sepsis remains to be elucidated. In this study, we retrieved transcriptomic profile data of septic patients and healthy donors and compared the expression level of METTL7B between septic patients and healthy controls. We also collected septic patient samples to analyze METTL7B expression via RT-qPCR. Murine bone marrow-derived macrophages (BMDMs) were isolated and treated with incremental doses of LPS as an in vitro cell model. METTL7B was overexpressed or knocked down in BMDMs, and lipopolysaccharide (LPS)-mediated inflammatory cytokines production and macrophage polarization were evaluated. We found that METTL7B was upregulated in the blood and peripheral blood mononuclear cells (PBMC) of septic patients, which also showed a significant diagnostic potential for sepsis. In BMDMs, METTL7B was induced in a time and dose-dependent manner by LPS. Modulating the expression level of METTL7B could regulate LPS-mediated inflammatory cytokines production and macrophage polarization. The functional role of METTL7B was also validated in a septic mouse model. Our findings indicate that METTL7B is implicated in the immunopathogenesis of sepsis through modulating macrophage-mediated inflammatory responses. METTL7B may serve as a potential diagnostic and therapeutic target for sepsis.