The balance between intrahepatic IL-17+ T cells and Foxp3+ regulatory T cells plays an important role in HBV-related end-stage liver disease

BACKGROUND: IL-17(+) T helper cells and Foxp3(+) regulatory T cells are CD4(+) T helper cells with reciprocally regulated differentiation and function. Their frequency and function vary in patients with chronic hepatitis B. In this study, we investigated the balance between IL-17(+) T cells and Foxp3(+) regulatory T cells and illustrated their function in the aggravation of chronic hepatitis B (CHB). RESULTS: Twenty-six patients with chronic HBV -related liver failure (CLF), thirty-one patients with acute on chronic HBV-related liver failure (ACLF) and twelve normal controls were enrolled in our study. The expressions of IL-17, Foxp3, CD4, CD8 and perforin in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. The frequency of liver IL-17(+) T cells on liver inflammatory cells and their proportion in the total CD4(+) T cell population increased markedly in the ACLF group, while the frquency of Foxp3+ T cells and their proportion in the total CD4(+) T cell population did not show a significant difference in the two HBV infection groups. In addition, the ACLF group showed a dramatically higher IL-17(+) /Foxp3(+) ratio than the CLF group. CD4(+) T cells increased significantly in the liver of patients with ACLF, compared with those in the liver of patients with CLF. CONCLUSIONS: Our findings suggest that intrahepatic IL-17(+) T cells play an important role in the development of chronic HBV and that the imbalance between IL-17(+) and Foxp3(+) T cells in the liver may lead to progression of the disease but the mechanism should be further explored.