PDF(Pubmed)
Abstract：
The balance between memory Th17 cells (mTh17) and memory Treg cells (mTreg) plays a key role in the pathogenesis of ulcerative colitis (UC), and TIGIT signaling is involved in the differentiation of mTh17/mTreg cells. Astragalus polysaccharide (APS) has good immunomodulatory and anti-inflammatory effects. Here, the regulatory effects and potential mechanisms of APS on mTh17/mTreg cells in UC are explored. A UC model was induced with dextran sulfate sodium (DSS) and treated simultaneously with APS (200 mg/kg/day) for 10 days. After APS treatment, the mice showed a significant increase in colonic length and a significant decrease in colonic weight, colonic weight index and colonic weight/colonic length, and more intact mucosa and lighter inflammatory cell infiltration. Notably, APS significantly down-regulated the percentages of Th17 (CD4+CCR6+), cmTh17 (CD4+CCR7+CCR6+) and emTh17 (CD4+CCR7-CCR6+) cells and significantly up-regulated the percentages of cmTreg (CD4+CCR7+Foxp3+) and emTreg (CD4+CCR7-Foxp3+) cells in the mesenteric lymph nodes of the colitis mice. Importantly, APS reversed the expression changes in the TIGIT molecule on mTh17/mTreg cells in the colitis mice with fewer CD4+CCR6+TIGIT+, CD4+CCR7-CCR6+TIGIT+ and CD4+CCR7-CCR6+TIGIT+ cells and more CD4+Foxp3+TIGIT+, CD4+CCR7-Foxp3+TIGIT+ and CD4+CCR7-Foxp3+TIGIT+ cells. Meanwhile, APS significantly inhibited the protein expression of the TIGIT ligands CD155, CD113 and CD112 and downstream proteins PI3K and AKT in the colon tissues of the colitis mice. In conclusion, APS effectively alleviated DSS-induced UC in mice by regulating the balance between mTh17/mTreg cells, which was mainly achieved through regulation of the TIGIT/CD155 signaling pathway.
摘要：
记忆Th17细胞(mTh17)和记忆Treg细胞(mTreg)之间的平衡在溃疡性结肠炎(UC)的发病机制中起关键作用,和TIGIT信号参与mTh17/mTreg细胞的分化。黄芪多糖(APS)具有良好的免疫调节和抗炎作用。这里,探讨APS对UCmTh17/mTreg细胞的调控作用及其可能的机制。用葡聚糖硫酸钠(DSS)诱导UC模型,并用APS(200mg/kg/天)同时处理10天。APS治疗后,小鼠结肠长度显着增加，结肠重量显着降低，结肠重量指数和结肠重量/结肠长度，更完整的粘膜和较轻的炎症细胞浸润。值得注意的是,APS显著下调Th17（CD4+CCR6+）的百分比，cmTh17(CD4+CCR7+CCR6+)和emTh17(CD4+CCR7-CCR6+)细胞,并显著上调结肠炎小鼠肠系膜淋巴结中cmTreg(CD4+CCR7+Foxp3+)和emTreg(CD4+CCR7-Foxp3+)细胞的百分比。重要的是,APS逆转了CD4+CCR6+TIGIT+结肠炎小鼠mTh17/mTreg细胞上TIGIT分子的表达变化,CD4+CCR7-CCR6+TIGIT+和CD4+CCR7-CCR6+TIGIT+细胞和更多的CD4+Foxp3+TIGIT+，CD4+CCR7-Foxp3+TIGIT+和CD4+CCR7-Foxp3+TIGIT+细胞。同时,APS显著抑制结肠炎小鼠结肠组织中TIGIT配体CD155、CD113和CD112以及下游蛋白PI3K和AKT的蛋白表达。总之,APS通过调节mTh17/mTreg细胞之间的平衡，有效缓解DSS诱导的小鼠UC，这主要是通过调节TIGIT/CD155信号通路来实现的。
