Mechanism of Sishen-Pill-Regulated Special Memory T and mTfh Cell via Involving JAK/STAT5 Pathway in Colitis Mice.

Abstract

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 β-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.