GBP1 promotes acute rejection after liver transplantation by inducing Kupffer cells pyroptosis

Biochim Biophys Acta Mol Basis Dis. 2024 Dec 26:167644. doi: 10.1016/j.bbadis.2024.167644. Online ahead of print.

Abstract

Liver transplantation is currently recognized as the most effective treatment for severe liver diseases. Although survival rates after liver transplantation have improved, rejection of the transplanted liver remains a significant cause of morbidity and transplant failure in patients. Our team previously discovered a close association between high GBP1 expression and acute rejection reactions following liver transplantation. Liver biopsies were conducted on patients who experienced acute rejection or successfully achieved immune tolerance post-transplantation. We confirmed that GBP1 was highly expressed in the acute rejection group after transplantation by Immunohistochemistry. This study aims to confirm that GBP1 promotes acute rejection reactions following liver transplantation through inducing pyroptosis in rat transplanted hepatic macrophages (KCs). We knocked down GBP1 in KCs and examined the extent of pyroptosis and the severity of acute rejection in the transplanted liver post-orthotopic liver transplantation in rats and KCs. These data provide new approaches for the study of liver transplant rejection reactions and identify new targets.

Keywords: GBP1; Kupffer cell; Liver transplantation; Pyroptosis.