Impact of TRAIL deficiency on Th17 cells in the mice experimental colitis induced by dextran sodium sulphate

Objective To investigate the impact of TNF-related apoptosis-inducing ligand (TRAIL) gene knock-out (TRAIL-/-) on Th17 cells in the mice colitis induced by dextran sulphate sodium (DSS). Methods Mice were randomly assigned to 4 subgroups: wild type (WT), TRAIL-/-, WT colitis and TRAIL-/-colitis (n=6/group). Colitis was induced by oral administration of 3.5% DSS for 7 consecutive days. The severity of colitis in each mouse was scored both clinically and histopathologically. Flow cytometry was performed to assess Th17 cell population in peripheral blood mononuclear cells (PBMC) and mesenteric lymph nodes (MLN). The expression levels of Th17 cell markers interleukin (IL)-17A and retinoic acid-related orphan receptor (ROR)-γt in PBMC and MLN were also examined using a quantitative polymerase chain reaction method. Results Compared with WT group, WT colitis group displayed elevated CD4+IL-17A+ Th17 cells (0.29±0.07 vs 0.08±0.03, 1.20±0.36 vs 0.40±0.11, both P<0.05) and enhanced mRNA expression of IL-17A and ROR-γt in PBMC and MLN (IL-17A: 2.43±0.87 vs 0.37±0.19, 5.03±1.77 vs 1.05±0.48, both P<0.05; ROR-γt: 2.49±0.48 vs 0.93±0.47, 23.75±7.60 vs 1.31±0.90, both P<0.05). After the DSS administration, TRAIL-/- group developed more severe colitis than WT group, mainly manifesting higher disease activity index, reduction of colon length and increased infiltration of inflammatory cells. In addition, TRAIL-/- colitis group exhibited increased proportion of CD4+ IL-17A+ Th17 cells (0.57±0.22 vs 0.29±0.07, P<0.001; 2.92±0.98 vs 1.20±0.36, P<0.000 1) as well as enhanced mRNA expression of IL-17A and ROR-γt in PBMC and MLN when compared with WT colitis group (IL-17A: 4.10±1.96 vs 2.43±0.87, 15.88±2.86 vs 5.03±1.77, both P<0.05; ROR-γt: 4.05±0.62 vs 2.49±0.48, 69.61±10.48 vs 23.75±7.60, both P<0.05). Conclusions TRAIL deficiency not only promots the number and activity of Th17 cells in PBMC and in MLN, but also aggravats DSS-induced colitis in mice. Key words: TNF-related apoptosis-inducing ligand; Colitis; Th17 cells