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成人社区获得性肺炎患者外周血髓源性抑制细胞亚群分布及程序性死亡受体-1/程序性死亡配体 1 轴的上调。

The distribution of myeloid-derived suppressor cells subsets and up-regulation of programmed death-1/PD-L1 axis in peripheral blood of adult CAP patients.

机构信息

Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Qingdao University Medical College, Qingdao, China.

Department of Respiratory and Critical Care Medicine, Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.

出版信息

PLoS One. 2023 Sep 27;18(9):e0291455. doi: 10.1371/journal.pone.0291455. eCollection 2023.

DOI:10.1371/journal.pone.0291455
PMID:37756307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10529571/
Abstract

BACKGROUND

Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP).

METHODS

This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis.

RESULTS

Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients.

CONCLUSIONS

In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.

摘要

背景

髓系来源抑制细胞(MDSCs)已被报道在恶性肿瘤和感染性疾病中扩增,并具有强大的扩增调节性 T 细胞的能力。本研究旨在探讨 MDSCs 及其可能的免疫机制在抑制社区获得性肺炎(CAP)免疫反应中的作用。

方法

这是一项单中心横断面研究。通过流式细胞术分析测定成人 CAP 患者和健康对照者外周血中 MDSCs 亚群、MDSCs 亚群 PD-1/PD-L1(L2)水平和 Tregs 的分布。

结果

63 例成人 CAP 患者的外周血单个核细胞(PBMCs)中,G-MDSC(4.92±0.30 比 2.25±0.21,p<0.0001)和 M-MDSC(19.40±1.30 比 9.64±0.57,p<0.001)的频率均升高。CAP 患者外周血 Treg 表达 PD-1 和 CTLA-4 增加,但其频率无差异。此外,还发现 CAP 患者外周血 MDSC 亚群的 PD-L1 表达上调。值得注意的是,循环 MDSC 亚群的频率与 CAP 患者血液中性粒细胞计数百分比呈正相关。

结论

综上所述,CAP 患者循环 MDSC 亚群的显著扩增和 PD-1/PD-L1 水平的上调提示 PD-1/PD-L1 轴可能至少部分参与了 CAP 患者中 MDSC 介导的 Treg 免疫调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/fe3a4d493f61/pone.0291455.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/bcf8fe6eeaf0/pone.0291455.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/feace923085d/pone.0291455.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/149d3350beae/pone.0291455.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/fe3a4d493f61/pone.0291455.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/bcf8fe6eeaf0/pone.0291455.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/feace923085d/pone.0291455.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/149d3350beae/pone.0291455.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14de/10529571/fe3a4d493f61/pone.0291455.g004.jpg

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