Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages.
Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages.
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可溶性 PD-L1 通过减少单核细胞来源的巨噬细胞改善直接 ARDS
DOI：
10.1038/s41419-020-03139-9
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发表时间：
2020-10-30
影响因子：
9
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Xu J;Wang J;Wang X;Tan R;Qi X;Liu Z;Qu H;Pan T;Zhan Q;Zuo Y;Yang W;Liu J
急性呼吸窘迫综合征（ARDS）是重症监护病房（ICU）的常见病，虽然它与高死亡率相关，但目前没有有效的药物治疗。尽管对程序性细胞死亡蛋白1（PD-1）和PD-配体1（PD-L1）轴在ARDS中的作用了解甚少，但可能为ARDS后发生的免疫抑制机制提供重要见解。在本研究中，我们观察到直接ARDS幸存者中可溶性PD-L1（sPD-L1）（PD-1通路的潜在激活剂）的水平比非幸存者上调。sPD-L1可减轻急性呼吸窘迫综合征小鼠的炎性肺损伤，提高存活率，提示sPD-L1对急性呼吸窘迫综合征具有保护作用。使用高通量质谱细胞术，我们发现肺单核细胞衍生的巨噬细胞（MDM）的数量显着减少，促炎标志物，sPD-L1的保护作用减弱，在ARDS小鼠单核细胞/巨噬细胞耗竭。此外，PD-1表达在患有直接ARDS的患者和小鼠的MDM中增加。最后，我们发现sPD-L1在直接ARDS患者中诱导MDM细胞凋亡。综上所述，我们的结果表明，sPD-L1对表达PD-1的巨噬细胞的参与导致促炎性巨噬细胞的减少，并最终改善了直接ARDS。我们的研究确定了直接ARDS患者的预后指标和直接ARDS治疗发展的潜在靶点。
Acute respiratory distress syndrome (ARDS) is common in intensive care units (ICUs), although it is associated with high mortality, no effective pharmacological treatments are currently available. Despite being poorly understood, the role of programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) axis in ARDS may provide significant insights into the immunosuppressive mechanisms that occur after ARDS. In the present study, we observed that the level of soluble PD-L1 (sPD-L1), a potential activator of the PD-1 pathway, was upregulated in survivors of direct ARDS than in non-survivors. Administration of sPD-L1 in mice with direct ARDS relieved inflammatory lung injury and improved the survival rate, indicating the protective role of sPD-L1 in direct ARDS. Using high-throughput mass cytometry, we found a marked decrease in the number of lung monocyte-derived macrophages (MDMs) with proinflammatory markers, and the protective role of sPD-L1 diminished in ARDS mice with monocyte/macrophage depletion. Furthermore, PD-1 expression increased in the MDMs of patients and mice with direct ARDS. Finally, we showed that sPD-L1 induced MDM apoptosis in patients with direct ARDS. Taken together, our results demonstrated that the engagement of sPD-L1 on PD-1 expressing macrophages resulted in a decrease in pro-inflammatory macrophages and eventually improved direct ARDS. Our study identified a prognostic indicator for patients with direct ARDS and a potential target for therapeutic development in direct ARDS.
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影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
Picker, LJ
DOI：
10.1073/pnas.0809422106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Huang, Xin;Venet, Fabienne;Ayala, Alfred
通讯作者：
Ayala, Alfred
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
9
作者：
Channappanavar R;Perlman S
通讯作者：
Perlman S
循环单核细胞的消耗抑制 LPS 诱导的急性肺损伤小鼠中 IL-17 和 HMGB1 的表达
DOI：
10.1152/ajplung.00389.2016
发表时间：
2017-02-01
影响因子：
4.9
作者：
Jiang, Zhilong;Zhou, Qianlin;Zhu, Lei
通讯作者：
Zhu, Lei