Wuweixiaoduyin regulates TAZ-mediated immunoregulatory properties of Treg/TH17 cells in chronic osteomyelitis

Abstract

ABSTRACT Wuwei xiaoduyin (WWXDY) is a prescription for Chronic osteomyelitis (COM) in traditional Chinese medicine (TCM). However, its specific mechanism remains unclear. The objective of this study was to investigate the mechanism of WWXDY in COM treatment. To clarify the potential role of TAZ in the treatment of COM by WWXDY via regulatory CD4+ T cells differentiation. The expressions of TAZ, RORγt and Foxp3 were determined by Quantitative Real-time PCR and Western blot. Besides, levels of IL-21, IL-17 and IL-10 in peripheral blood were detected by using ELISA. Molecular dynamics simulations and docking were further utilized to explore the binding mechanism. COM resulted in abnormal cell differentiation and an imbalance of Treg/Th17. In comparison with the control group, the percentage of Treg cells, Foxp3 expression and secretion of IL-17 and −21 cytokines decreased (P < 0.001), while the proportion of Th17 cells, the levels of TAZ and RORγt and concentration of IL-10 in PBMCs increased in the COM group (P < 0.001). Furthermore, the above abnormal differentiation and function of Treg/Th17 cells in COM were suppressed after treatment with WWXDY in vivo and in vitro. In addition, TEAD1 inhibited the therapeutic effect of WWXDY in terms of Treg/Th17 cells with COM. it was found that the main active ingredients were cichoric acid and isocarlinoside. WWXDY regulates immunoregulatory properties of Treg/Th17 cells in COM mainly by mediating TAZ expression. By inhibiting the chronic inflammation in COM, WWXDY is potentially used to inhibit the progression of COM into bone tumors.