IL-2 improves dextran sulfate sodium-induced mouse model of inflammatory bowel disease by regulating CD4+ Treg

Abstract

Objective To investigate the effect of IL-2 on CD4+ regulatory cells (Treg) in inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium (DSS), and to explore its regulatory mechanism in the pathogenesis of IBD. Methods Wild type C57BL/6 (WT) and IL-2 knockout (IL-2-/-) female mice (both at 6 week old) were randomly divided into WT control group, WT DSS treatment group, and IL-2-/- control group and IL-2-/- DSS treatment group, respectively. The mice in the control group had normal drinking water, and those in the treatment group had the water containing 25 g/L DSS. In 1 week after the continuous feeding, all mice were sacrificed and the whole colon was collected for intestinal pathological injury in each group by HE staining. The expression levels of IL-2, TGF-β, IL-10, IFN-γ and TNF-α at mRNA and protein levels were detected by PCR and Western blotting, respectively, and the percentage of CD4+ Treg were counted by flow cytometry. Results There were significant differences in the lesion, inflammation, lesion range and crypt destruction score among the 4 groups, and the pathological scores of colon tissue were the highest in the IL-2-/- DSS treatment group than the other 3 groups, and the scores were significantly higher in the WT DSS treatment group and IL-2-/- control group mice than the WT control group (P < 0.05). Significant differences were seen in the mRNA and protein levels of IL-2, TGF- β, IL-10, IFN-γ and TNF-α in the colon tissues from the 4 groups (P < 0.05). The mRNA and protein levels of IL-2, TGF-β and IL-10 in WT DSS treatment group were significantly higher than those in the other 3 groups, and the levels of IFN-γ and TNF-α in the IL-2-/- DSS treatment group were significantly higher than those in the other 3 groups (P < 0.05). After 7 days' treatment, the percentage of CD4+ Treg was significantly higher in WT DSS treatment group than the other 3 groups (P < 0.05). Conclusion IL-2 can improve DSS-induced IBD and reduce inflammatory response and colon tissue injury by inducing CD4+ Treg to secrete inhibitory inflammatory factors TGF- β and IL-10.

Keywords

• interleukin-2
• cd4+ treg
• dextran sulfate sodium
• inflammatory bowel disease