Wang Mengxue, Huang Xiaoying, Kang Zengping, Huang Jiaqi, Wei Siyi, Zhao Haimei, Zhong Youbao, Liu Duanyong
Graduate School, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi, China.
Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi, China.
Evid Based Complement Alternat Med. 2022 Mar 28;2022:6446674. doi: 10.1155/2022/6446674. eCollection 2022.
It is known that memory T cells (mT cell) and memory T follicular cells (mTfh) play vital roles in the IBD pathogenesis. Sishen Pill (SSP) is a classic prescription used to treat chronic ulcerative colitis (UC). However, it is still unclear whether SSP can regulate immune homeostasis induced by mT cell and mTfh to treat IBD. In this study, we measured mT cell and mTfh level to explore the conceivable mechanism of SSP-treated IBD. The mice colitis were induced by dextran sulfate sodium (DSS) and were treated by SSP for 7 days. The therapeutic effect of SSP was evaluated by macroscopic and microscopic observation; the mT cell, mTfh, and their subsets were analyzed by flow cytometry. Activation of the JAK/STAT signaling pathway was analyzed by using a Western blot. In the present study, SSP significantly reversed weight loss and colonic injury (colon weight increase and colonic length shortening) caused by 3% DSS in physiological saline solution. Flow cytometry showed that the percentages of CD4 and CD8 expressions on central memory T cells were enhanced after SSP treatment, while the CD4 T cm, CD4 mTfh (memory T follicular helper) cells and their subpopulations were also significantly increased. Moreover, SSP inhibited the expression of JAK/STAT signaling pathway proteins JAK1, PIAS3, STAT5, p-STAT5, BIM, BAX, caspase-3, and -casein and promoted the expression of JAK3, PISA1, Bcl-2, and caveolin-1. In summary, SSP can regulate immune homeostasis induced by mT cell and mTfh in DSS-induced colitis, which is potentially correlated with JAK/STAT signaling pathway activation.
已知记忆T细胞（mT细胞）和记忆性滤泡辅助性T细胞（mTfh）在炎症性肠病（IBD）发病机制中发挥着至关重要的作用。四神丸（SSP）是用于治疗慢性溃疡性结肠炎（UC）的经典方剂。然而，SSP是否能够通过调节由mT细胞和mTfh诱导的免疫稳态来治疗IBD仍不清楚。在本研究中，我们检测了mT细胞和mTfh水平，以探究SSP治疗IBD可能的机制。通过葡聚糖硫酸钠（DSS）诱导小鼠结肠炎，并给予SSP治疗7天。通过大体和显微镜观察评估SSP的治疗效果；采用流式细胞术分析mT细胞、mTfh及其亚群。使用蛋白质免疫印迹法分析JAK/STAT信号通路的激活情况。在本研究中，SSP显著逆转了由生理盐水中3% DSS引起的体重减轻和结肠损伤（结肠重量增加和结肠长度缩短）。流式细胞术显示，SSP治疗后，中央记忆T细胞上CD4和CD8的表达百分比增加，而CD4 Tcm、CD4 mTfh（记忆性滤泡辅助性T细胞）及其亚群也显著增加。此外，SSP抑制JAK/STAT信号通路蛋白JAK1、PIAS3、STAT5、p-STAT5、BIM、BAX、caspase-3和β-酪蛋白的表达，并促进JAK3、PISA1、Bcl-2和小窝蛋白-1的表达。综上所述，SSP可调节DSS诱导的结肠炎中由mT细胞和mTfh诱导的免疫稳态，这可能与JAK/STAT信号通路激活有关。
