Chen Yueyue, Wang Yue, Xu Lei, Zhu Weina, Xu Changsong, Xu Meimei, Guo Liang, Hu Wei, Xu Dake, Jing Rongyue, Zhu Yamei, He Jing, Xu Bo
Department of Immunology and Rheumatology, Third affiliated hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Department of First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Int J Rheum Dis. 2019 Feb;22(2):200-206. doi: 10.1111/1756-185X.13391. Epub 2018 Oct 18.
To study the influence of total glucosides of paeony (TGP) on the expression of peripheral blood programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in patients with primary Sjögren's syndrome (pSS).
Ten patients with new-onset pSS were selected as the experimental group and were treated with 1.8 g of TGP (the main ingredient is Radix Paeoniae Alba) daily for 3 months; furthermore, 10 physically healthy individuals were selected as the control group. Peripheral blood mononuclear cells were isolated, and flow cytometry was used to detect PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes and PD-L1 expression on the surface of CD14+ monocytes and CD19+ B cells before and after treatment in the experimental and control groups. Furthermore, plasma levels of soluble PD-1 (sPD-1), interleukin (IL)-10, and IL-17A were also determined using enzyme-linked immunosorbent assay.
The PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes in the peripheral blood of patients with pSS were significantly higher than in the control group (P < 0.001). However, PD-L1 expression on the surface of CD14+ monocytes declined but not significantly (P > 0.05), and PD-L1 expression on the surface of CD19+ B cells increased significantly (P < 0.001). Moreover, sPD-1 and IL-17A levels in the plasma of the experimental group were significantly higher than in the control group (P < 0.001), but the IL-10 level was significantly lower than in the control group (P < 0.001). After TGP treatment, PD-1 expression on the surface of CD4+ T and CD8+ lymphocytes in the peripheral blood of patients with pSS had decreased significantly (P < 0.001); the PD-L1 expression on the surface of CD19+ cells had decreased significantly (P < 0.001); and the PD-L1 expression on the surface of CD14+ monocytes did not differ significantly (P > 0.05). Furthermore, the levels of sPD-1 and IL-17A in plasma had decreased (P < 0.01) and IL-10 levels had increased after TGP treatment (P < 0.01).
PD-1/PD-L1 molecules expressed on the surface of T cells, B cells, and monokaryon participated in the pathogenesis and development of SS through interactions. Therefore, TGP, which may increase the expression of PD-1 and its relevant ligand PD-L1 in the peripheral blood mononuclear cells, may play a role in the pathogenesis and development of SS through the PD-1/PD-L1 pathway by regulating regulatory T cells/T helper cell 17.
研究芍药总苷（TGP）对原发性干燥综合征（pSS）患者外周血程序性细胞死亡蛋白1（PD-1）及其配体（PD-L1）表达的影响。
选取10例新发pSS患者作为实验组，每日给予1.8 g TGP（主要成分为白芍）治疗3个月；另选取10名身体健康者作为对照组。分离外周血单个核细胞，采用流式细胞术检测实验组和对照组治疗前后CD4⁺T淋巴细胞和CD8⁺T淋巴细胞表面PD-1表达以及CD14⁺单核细胞和CD19⁺B细胞表面PD-L1表达。此外，还采用酶联免疫吸附测定法测定血浆可溶性PD-1（sPD-1）、白细胞介素（IL）-10和IL-17A水平。
pSS患者外周血CD4⁺T淋巴细胞和CD8⁺T淋巴细胞表面PD-1表达显著高于对照组（P<0.001）。然而，CD14⁺单核细胞表面PD-L1表达有所下降，但差异不显著（P>0.05），而CD19⁺B细胞表面PD-L1表达显著升高（P<0.001）。此外，实验组血浆中sPD-1和IL-17A水平显著高于对照组（P<0.001），但IL-10水平显著低于对照组（P<0.001）。TGP治疗后，pSS患者外周血CD4⁺T淋巴细胞和CD8⁺淋巴细胞表面PD-1表达显著降低（P<0.001）；CD19⁺细胞表面PD-L1表达显著降低（P<0.001）；CD14⁺单核细胞表面PD-L1表达差异不显著（P>0.05）。此外，TGP治疗后血浆中sPD-1和IL-17A水平降低（P<0.01），IL-10水平升高（P<0.01）。
T细胞、B细胞和单核细胞表面表达的PD-通过相互作用参与了干燥综合征的发病机制和发展过程。因此，可能增加外周血单个核细胞中PD-1及其相关配体PD-L1表达的TGP，可能通过调节调节性T细胞/辅助性T细胞17，经由PD-1/PD-L1途径在干燥综合征的发病机制和发展过程中发挥作用。
