Abstract
Currently, it is unclear whether Sishen Wan (SSW) could modulate the balance of Th1 cells, Th17 cells, and Tregs and we evaluated the effects of SSW on T cell responses in mice models of ulcerative colitis (UC). The mice models of acute UC (4% dextran sodium sulfate (DSS), 8 days) and chronic UC (3% DSS, 16 days) with SSW were assayed. Colon tissues were collected for immunohistochemical analysis, enzyme linked immunosorbent assay (ELISA), and flow cytometry (FCM). The expressions of cytokines associated with Tregs, transcription factors of Th17 cells, the frequencies of Th1 cells, Th17 cells, and Tregs, and the functional plasticity of Th17 cells were detected. The frequency of IFN-γ+ T cells was not changed significantly with SSW treatment in acute DSS. In chronic models, the frequency of IFN-γ+ T cells was downregulated with SSW. Meanwhile, the levels of RORγt and the frequency of IL-17A+ Th17 cells showed no significant differences after SSW treatment. Despite no significant effect on the transdifferentiation of Th17 cells in chronic UC models, SSW transdifferentiated Th17 cells into IL-10+ Th17 cells and downregulated IFN-γ+ Th17 cells/IL-10+ Th17 cells in acute DSS. Moreover, there were no significant changes of cytokines secreted by Tregs in acute DSS after SSW treatment, but SSW facilitated the expressions of IL-10 and IL-35, as well as development of IL-10+ Tregs in chronic DSS. SSW showed depressive effects on the immunoreaction of Th17 cells and might promote the conversion of Th17 cells into IL-10+ Th17 cells in acute UC, while it inhibited the excessive reaction of Th1 cells, facilitated the development of Tregs, and enhanced the anti-inflammatory effects in chronic UC.
Highlights
Ulcerative colitis (UC), a common chronic nonspecific inflammatory bowel disease (IBD), is generally manifested as diarrhea, abdominal pain, weight loss, and hematochezia [1, 2]
Significant upregulation in the percentages of IFN-c+ T cells and IL-17A+ T cells were observed in acute DSS and chronic DSS (P < 0.01). e percentages of IL-17A+ T cells were significantly lower with Sishen Wan (SSW) in acute DSS, whereas there was no significant tendency of downregulation in the percentage of 1 cells
Our results suggested that the levels of some inhibitory cytokines were increased in acute DSS. ere were no significant effects on the contents of IL-10, TGF-β, and IL-35 in acute DSS treated with SSW, which might be due to the fact that the efficacy of SSW had no obvious correlation with inhibitory cytokines derived from Tregs. e level of IL-10 was upregulated significantly in chronic UC models, while the levels of TGF-β and IL-35 had no obvious variations
Summary
Ulcerative colitis (UC), a common chronic nonspecific inflammatory bowel disease (IBD), is generally manifested as diarrhea, abdominal pain, weight loss, and hematochezia [1, 2]. The prevalence of UC is increasing worldwide. It is commonly recognized that extensive and long-standing UC poses a substantial cancer risk and the risk for colitis-associated colorectal cancer (CAC) was reported to be around 30% at 35 years after the onset of the disease [3, 4]. Current therapeutic options used for the treatment against UC include 5-aminosalicylate, glucocorticoid, and immunosuppressive agents. These available treatments are accompanied with significant adverse gastrointestinal reactions, serious complications such as tuberculosis, recurrence, and a heavy economic burden [8,9,10]. It is of vital importance to explore a series of novel, safe, and efficient methods for the treatment of UC
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