Double-Negative T Cells Promote Liver Fibrosis Progression by Regulating Treg/Th17.

Abstract

We investigated the mechanism whereby double-negative T cells (DNTs) regulate Treg/Th17 balance to promote the progression of liver fibrosis. Liver fibrosis was induced with carbon tetrachloride (CCl4) in mice. Mouse DNTs were isolated, amplified and injected. The proportions of iTreg (CDF4+CD25+Foxp3+) and Th17 (CD4+IL-17A+) in peripheral mononuclear cells, spleen and liver were analyzed by flow cytometry, and the cytokine levels were determined through enzyme-linked immunosorbent assay (ELISA). DNTs could promote the Th17 differentiation and inhibit the iTreg differentiation. The role of DNTs in promoting liver fibrosis progression and tissue inflammation was exerted through activation of IκBa. The use of IL-17A monoclonal antibody enabled suppression of the DNTs effects, reduction of the Th17 proportion and alleviation of liver fibrosis. Hal could suppress the Th17 differentiation and the effect of DNTs. DNTs can promote the Th17 differentiation through IL-17A and inhibit iTreg differentiation, thereby facilitating the liver fibrosis progression and microenvironmental inflammation. DNTs are a kind of important immunocytes that promote the liver fibrosis progression.