Role Of KLRG1 Expressing Lymphocytes In Primary Biliary Cholangitis

Backgrounds:Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by non-purulent destructive cholangitis of the hepatic interlobular bile ducts.Different degrees of liver fibrosis and even liver cirrhosis may emerge during the disease progression.The immune damage of cytotoxic T lymphocytes to biliary epithelial cells plays an extremely important role in the occurrence and development of PBC.PartⅠ Cytotoxic KLRG1 expressing lymphocytes participate in immune-mediated bile duct injury in patients with PBCObjective:To investigate the number and subtypes of hepatic KLRG1 expressing cells in PBC patients and its correlation with clinical index.To study the potential mechanisms of KLRG1 expressing lymphocytes involved in bile duct injury.Methods:Gene expression data(GSE79850)from PBC(n=16)and normal(n=8)liver biopsies were analyzed for cytotoxic T cell differentiation status,with stratification according to risk of liver transplantation.Immunohistochemistry,confocal microscopy and flow cytometry were used to investigate the frequency,phenotypic,functional characteristics of KLRG1 positive cells in liver and peripheral blood as well as the expression of E-cadherin,the inhibitory ligand for KLRG1,in PBC patients.Results:PBC patients with high KLRG1 expression in the liver had a significantly higher risk of liver transplantation within 15 years.A great proportion of inflammatory cells that infiltrated liver tissues were KLRG1~+cells,especially CD8~+KLRG1~+T cells.Most of the KLRG1~+cells infiltration in the liver portal area,with a tendency to localize around the injured bile duct.Hepatic KLRG1~+cells were significantly positively correlated with hepatic inflammation degree,liver fibrosis grade,and PBC-related biochemical markers.The peripheral blood KLRG1~+lymphocytes of PBC patients have stronger cytotoxicity and higher expression levels of chemokines than KLRG1~–counterparts.In addition,E-cadherin,the inhibitory ligand for KLRG1,partially disappeared in the intrahepatic small bile duct of PBC patients.Conclusions:Cytotoxic KLRG1 expressing lymphocytes from peripheral blood of PBC patients maybe be chemotaxis to the portal area by expressing chemokine receptors,and mediate autoimmune damage to biliary epithelial cells lacking E-cadherin.PartⅡ Serum CTHRC1 level predicts intrahepatic histopathology in PBC patientsObjective:To explore the serum CTHRC1 levels in PBC patients and its predictive value for pathological characteristics of liver.Methods:Serum levels of CTHRC1 protein in PBC patients was detected by ELISA.Results:Serum CTHRC1 protein levels in PBC patients was positively correlated with the hepatic inflammatory and liver fibrosis.It also had certain predictive value for liver cirrhosis in patients with PBC.Conclusions:Serum CTHRC1 protein levels help assess hepatic pathological conditions in patients with PBC.