Unbalanced expression of membrane-bound and soluble programmed cell death 1 and programmed cell death ligand 1 in systemic juvenile idiopathic arthritis

Unbalanced expression of membrane-bound and soluble programmed cell death 1 and programmed cell death ligand 1 in systemic juvenile idiopathic arthritis
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系统性幼年特发性关节炎中膜结合型和可溶性程序性细胞死亡 1 和程序性细胞死亡配体 1 的不平衡表达

DOI:
10.1016/j.clim.2021.108800
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发表时间:
2021-07-21
影响因子:
8.6
通讯作者:
Chen, Tongxin
Chen, Tongxin
中科院分区:
医学3区
文献类型:
--
作者:
Cai, Li;Zhang, Chenxing;Chen, Tongxin

文献摘要

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本研究旨在探讨系统性幼年特发性关节炎(SJIA)患者血清中可溶性程序性死亡-1(Spd-1)及其配体(Spd-L1)的水平及其免疫调节机制。采用双抗体夹心法和Luminex法检测血浆SPD-1、SPD-L1及相关细胞因子和蛋白水平。流式细胞仪检测PD-1/PD-L1信号对髓系树突状细胞(MDC)和IL-6分泌的影响。结果表明,sJIA患者SPD-1水平降低与JADAS-27、PGA、PtGA、CRP呈负相关。SJIA患者MDC表面CD86和MHC-II表达水平较低。阻断PD-1/PD-L1信号后,DC分泌IL-6增加。我们的发现表明,Spd-1表达下调与临床指标有关,可能成为诊断sJIA的新的生物标志物。PD-1/PD-L1膜的减少和可溶性可能通过促进MDC的增殖和IL-6的分泌参与了sJIA的发病。
The study aimed to investigate the soluble programmed death-1 (sPD-1) and its ligand (sPD-L1) levels in systemic juvenile idiopathic arthritis (sJIA) patients and elucidate its underlying immunomodulatory mechanisms. Plasma levels of sPD-1, sPD-L1 and related cytokines and proteins were detected using an enzyme-linked immunosorbent assay (ELISA) and Luminex. The effects of PD-1/PD-L1 signal on mDC (myeloid dendritic cell) and IL-6 secretion were measured using flow cytometry. The results revealed decreased levels of sPD-1 in sJIA patients negatively correlated with JADAS-27, PGA, PtGA and CRP. sJIA patients had lower CD86 and MHC-II expression on mDC. When blocking PD-1/PD-L1 signal, IL-6 secretion of DC were increased. Our finding displayed downregulated sPD-1 was related with clinical indicators and could be a new biomarker for sJIA diagnosis. The reduced membrane and soluble forms of PD-1/PD-L1 might take part in sJIA pathogenesis by enhancing mDC proliferation and IL-6 secretion.