NLRP6 deficiency aggravates liver injury after allogeneic hematopoietic stem cell transplantation

This study aims to observe the expression and role of NLRP6 in liver injury after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Allo-HSCT model was established through infusion of 5 × 10⁶ bone marrow mononuclear cells into whole body irradiated mice. On days 7, 14, 21 and 28 after transplantation, the peripheral blood was collected to detect liver function. The liver of the mice was obtained to assess the pathological changes of liver tissues after allo-HSCT by H&E staining and Mason staining. Meanwhile, expression of NLRP6, phosphorylated p38-MAPK and IκBα, caspase-1 and NLRP3 in liver were detected by Western blot. ELISA was used for detection of the level of interleukin (IL)-1β, IL-18, tumor necrosis factor (TNF)-α, IL-6, myeloperoxidase (MPO) and tumor growth factor (TGF)-β1. Increased expression of NLRP6, phosphorylated Iκbα, phosphorylated p38-MAPK, pro-caspase-1, and p20, in liver tissue with injury and fibrosis in mice after allo-HSCT were observed. Meanwhile, the level of IL-1β, IL-18, IL-6 and TNF-α was also increased. However, NLRP6^-/- mice showed more severe liver damage and liver fibrosis after transplantation together with higher level of phosphorylated Iκbα, phosphorylated p38-MAPK, Pro-caspase-1, p20 expression as well as IL-1β, IL-18, IL-6, and TNF-α secretion compared with wide-type. Interestingly, the expression of NLRP3 in the liver of NLRP6^-/- mice was significantly higher than that of wild-type. In conclusion, the expression of NLRP6 in host's liver is associated with liver injury after allo-HSCT. NLRP6 deficiency in host's liver leads to more severe liver damage, indicating a protective role of NLRP6 in host's liver to liver damage after allo-HSCT.