Objective:To investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.

Objective:To investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.