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In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells.
Archivum Immunologiae et Therapiae Experimentalis ( IF 2.9 ) Pub Date : 2020-04-01 , DOI: 10.1007/s00005-020-00577-3
Chenchen Qin 1 , Huihui Liu 1 , Bo Tang 1 , Min Cao 1 , Zhengyu Yu 1 , Beichen Liu 1 , Wei Liu 1 , Yujun Dong 1 , Hanyun Ren 1
Affiliation  

AMG 487 is the targeted blocker of chemokine receptor CXCR3 and improves inflammatory symptoms by blocking the inflammatory cycle. Here we investigated whether AMG 487 affects dendritic cell (DC) biology and function. The expression of co-stimulatory markers on DCs was reduced, indicating the semi-mature state of DC when AMG 487 was added throughout the in vitro differentiation period. Additionally, when added solely during the final lipopolysaccharide-induced activation step, AMG 487 inhibited DC activation, as demonstrated by a decreased expression of activation markers. AMG487 also promoted the expression of PD-L2 and impaired the ability to induce antigen-specific T cell responses. Our results demonstrated that AMG 487 significantly affects DC maturity in vitro and function leading to impaired T cell activation, inducing DCs to have characteristics similar to tolerogenic DCs. AMG 487 may directly play an immunomodulatory role during DC development and functional shaping.

中文翻译:

CXCR3抑制剂AMG487对树突状细胞的体外免疫作用。

AMG 487是趋化因子受体CXCR3的靶向阻断剂,可通过阻断炎症周期来改善炎症症状。在这里,我们调查了AMG 487是否影响树突状细胞(DC)的生物学和功能。共刺激标志物在DC上的表达降低,表明当在整个体外分化期添加AMG 487时DC处于半成熟状态。另外,当仅在最后的脂多糖诱导的激活步骤中添加时,AMG 487抑制DC激活,如激活标记物表达降低所证明。AMG487还促进了PD-L2的表达并削弱了诱导抗原特异性T细胞反应的能力。我们的结果表明,AMG 487在体外显着影响DC的成熟度和功能,从而导致T细胞活化受损,诱导DC具有类似于致耐受DC的特性。AMG 487可能在DC发育和功能塑造过程中直接发挥免疫调节作用。
更新日期:2020-04-20
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