Total glucosides of paeony alleviates Sjogren's syndrome by inhibiting Th1 and Th17 responses.

BACKGROUND: Sjogren's syndrome (SS) is distinguished by immune cells infiltration of exocrine glands, with T helper (Th) cells playing a crucial role in its progression. Total glucosides of paeony (TGP), the main compounds of Chinese medicine Paeonia lactiflora Pall, can treat many autoimmune diseases including SS. PURPOSE: To explore the impact and mechanism of TGP on differentiation and functionality of Th1 and Th17 cells in the SS model, and to provide novel insights into potential therapeutic strategies for this condition. STUDY DESIGN: Non-Obese Diabetic (NOD) mice and spleenic naive CD4(+)T cells of mice were employed to detect the relevant molecules of Th1 and Th17 with TGP administration to elucidate the mechanism by which TGP affected SS through Th cell differentiation. METHODS: NOD mice were intragastrically administered with TGP (720, 360 mg/kg), Hydroxychloroquine (HCQ, 80 mg/kg), and Paeoniflorin (PF, 300 mg/kg) for 16 weeks, respectively. In vitro, naive CD4(+)T cells from spleen of mice were incubated with TGP (60, 30 mug/ml) and PF (25 mug/ml) for 3 days. The measurements were conducted on saliva flow, tear flow, as well as the pathology of submandibular glands (SMG) and lacrimal glands (LG). Flow cytometry was utilized to identify the percentage of Th1, Th17, and regulatory T cells (Treg) in peripheral blood CD4(+)T cells and naive CD4(+)T cells, respectively. Furthermore, the expression levels of factors related to Th1 and Th17 in SMG, LG and spleenic naive CD4(+)T cells were analyzed using RT-qPCR, ELISA, immunohistochemical staining as well as Western blotting. RESULTS: In comparison to NOD mice administered with vehicle, TGP treatment enhanced tear and saliva flow, ameliorated pathological damage in SMG and LG, down-regulated the percentages of Th1 and Th17 lymphocytes, and suppressed the expression of Th1 and Th17 cell-related factors in SMG and LG at both mRNA and protein levels. Moreover, TGP could prevent naive CD4(+)T cells from differentiating into Th1 and Th17 subsets by suppressing the mRNA and protein expression of Th1 and Th17 related factors, leading to a reduction of effector cytokines including IFN-gamma and IL-17A in the cell culture supernatant. CONCLUSION: TGP inhibits differentiation and function of Th1 and Th17 cells, which facilitates the amelioration of SS symptoms.