Sishen Pill Regulates Memory T Cells in Mice with Colitis via JAK/STAT 5 Signaling Pathway

Abstract Background: Memory T cell (Tm) has a pivotal role as host protection in autoimmune inflammatory diseases via a JAK/STAT signaling pathway. Sishen Pill (SSP) is a classic prescription used to treat chronic ulcerative colitis (UC). However, it is still unclear whether SSP can regulate immune memory function. In this study, we examined the effect of SSP and whether it can regulate immune memory function through a JAK/STAT5 signaling pathway.Methods: Mice were randomly divided into four groups (10 mice per group): Normal group (Normal), health mice without DSS administration; DSS group (DSS), mice with DSS administration; Sishen pill treated (DSS+SSP) group, colitis mice treated with SSP for 7 days; Mesalazine controlled (DSS+5-ASA) group, colitis mice treated with mesalazine for 7 days. The therapeutic effect of SSP was evaluated by macroscopic and microscopic observation; Tm and their subsets were analyzed by flow cytometry; Activation of the JAK/STAT signaling pathway was analyzed using a Western blot.Results: SSP significantly reversed weight loss and colonic injury (colon weight increase and colonic length shortening) caused by 3% dextran sodium sulfate (DSS). Flow cytometry showed that the percentages of CD4+ and CD8+ expressions on central memory T cells were enhanced after SSP treatment, while the CD4+ Tcm, CD4+ mTfh (memory T follicular helper) cells and their subpopulations were also significantly increased. Moreover, SSP inhibited the expression of STAT5 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. Conclusions: SSP can be used to effectively treat DSS-induced colitis by improving the status of immune memory via the JAK/STAT signaling pathway.