科研之友
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摘要
Background The outcome of hepatitis B virus (HBV) infection is significantly affected by host immune response; herein, we aim to dissect the effect of L-carnitine (L-Cn) on germinal center (GC)-related immune cells and the influence on the prognosis of HBV infection. Methods In vitro and in vivo experiments were performed in patients with chronic HBV infection and a hydrodynamic injection mouse model. Results In vitro assays revealed that L-Cn significantly reduced GC-related immune responses and enhanced immunosuppressive profiles. Intriguingly, L-Cn released from lysed hepatocytes was associated with the degree of liver damage. Besides, the administration of L-Cn in an HBV mouse model resulted in delayed clearance of hepatitis B surface antigen (HBsAg) in serum and decreased GC formation in the spleen. Notably, patients with HBsAg loss showed decreased plasma L-Cn levels, and longitudinal observations found that low baseline levels of L-Cn were associated with a favorable treatment response in patients with chronic hepatitis B. Conclusions The suppressive effect of hepatocyte-derived L-Cn on GC-related immune cells may contribute to the inability of HBsAg clearance in chronic HBV infection, indicating that L-Cn might serve as a potential therapeutic target for the treatment of HBV infection. @@@ Redundant L-carnitine released from injured hepatocytes inhibits hepatitis B surface antigen clearance, possibly by preventing germinal center (GC) formation, downregulating antiviral abilities of GC-related immune cells, and enhancing the function of immunosuppressive cells.
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单位南方医科大学
