Influence of TRAIL Deficiency on Th17 Cells and Colonic Microbiota in Experimental Colitis Mouse Model

Abstract

BackgroundThe abnormalities of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are implicated in various autoimmune disorders and tumors. This study investigated the influence of TRAIL deficiency on Th17 cells and colonic microbiota in experimental colitis mouse model. MethodsMice were randomly divided into 4 groups: wild-type, TRAIL gene knock-out (TRAIL−/−), wild-type colitis and TRAIL−/− colitis groups. Colitis was induced by oral administration of 3.5% dextran sulfate sodium (DSS) for 7 consecutive days. Mice were given scores for disease severity both clinically and histopathologically. Th17 cells in peripheral blood and mesenteric lymph nodes (MLNs) were assessed using flow cytometry. The expression levels of Th17 cell markers IL-17A and ROR-γt were evaluated by quantitative real-time polymerase chain reaction. The colonic samples were also analyzed for microbiota profile by 16s-rDNA gene sequencing on variable V4 region. ResultsCompared with wild-type counterparts, TRAIL−/− mice developed more severe colitis after DSS treatment. Colitis TRAIL−/− mice had increased proportion of Th17 cells and elevated mRNA expression levels of IL-17A and ROR-γt in peripheral blood and MLNs compared with colitis wild-type mice. In contrast to colitis wild-type mice, the composition of colonic microbiota was shifted in colitis TRAIL−/- mice, and was characterized by increased alpha diversity, increased TM7, deferribacteres and tenericutes, and decreased proteobacteria at the phylum level. ConclusionsThese findings suggested that TRAIL deficiency not only aggravated DSS-induced colitis, but also led to enhanced Th17 cell response and altered colonic microbiota composition.