Influence of Tumor Necrosis Factor-related Apoptosis-inducing Ligand on Balance of Th17 and Treg Cells in Mice With Experimental Colitis / 胃肠病学

ABSTRACT

Background: Imbalance of Th17/Treg cells might play a key role in the initiation of Crohn's disease (CD). Moreover, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway was suggested to be implicated in the pathogenesis of CD and other autoimmune diseases. Aims: To investigate the influence of TRAIL gene deletion on the balance of Th17 and Treg cells in mice with experimental colitis. Methods: TRAIL-/- C57BL/6 mice were obtained by CRISPR/Cas9 method. Then 20 TRAIL-/- mice and 20 wild-type (WT) mice were randomly divided into WT group, TRAIL-/- group, WT trinitrobenzenesulfonic acid (TNBS)-induced colitis group and TRAIL-/- TNBS-induced colitis group, with 10 mice in each group. The severity of colonic inflammation was assessed by disease activity index (DAI) and histology activity index (HAI). Peripheral blood and colonic tissue were collected to determine the expression levels of Th17 and Treg cell-associated transcription factors (RORγt, Foxp3) and cytokines [interleukin-17 (IL-17), IL-10] by real-time PCR, Western blotting and ELISA method, respectively. Results: Compared with untreated mice, mice with experimental colitis showed decreased body weight, shortened colon length as well as increased DAI and HAI (P<0.05), and the manifestations of colitis in TRAIL-/- mice were more serious than that in WT mice (P<0.05). In WT mice with experimental colitis, the expression levels of RORγt and IL-17 in peripheral blood and colonic tissue were significantly increased than those in untreated WT mice (P<0.05), while the expression levels of Foxp3 and IL-10 were significantly decreased (P<0.05). Furthermore, the expression levels of all four Th17 and Treg cell-associated molecules were higher in TRAIL-/- colitis mice than in WT colitis mice (P<0.05). In addition, the ratio of RORγt to Foxp3 were higher in TRAIL-/- colitis mice than in WT colitis mice (P<0.05). Conclusions: Deletion of TRAIL gene may aggravate the severity of colonic inflammation via up-regulating Th17/Treg ratio in mice with experimental colitis.