稳定期 COPD 患者外周血中程序性死亡受体-1/PD-L1 轴、髓系来源的抑制细胞亚群和调节性 T 细胞的临床相关性。
The clinical association of programmed death-1/PD-L1 axis, myeloid derived suppressor cells subsets and regulatory T cells in peripheral blood of stable COPD patients.
机构信息
Department of Respiratory and Critical Care Medicine, Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Affiliated Hospital of Qingdao University Medical College, Department of Respiratory and Critical Care Medicine, Qingdao, China.
出版信息
PeerJ. 2024 Mar 27;12:e16988. doi: 10.7717/peerj.16988. eCollection 2024.
BACKGROUND
Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients.
METHODS
Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood.
RESULTS
Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs ( < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs ( < 0.01) was detected in COPD patients. The expression of PD-1 on CD4 Tcells and Tregs, but not CD8Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs ( < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, < 0.0001) and CTLA-4 (r = 0.42, = 0.0014) on Tregs in COPD.
CONCLUSION
The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.
背景
髓系来源的抑制细胞（MDSCs）在各种疾病过程中T 细胞功能障碍中具有重要的免疫抑制作用。然而，MDSCs 的作用及其对 COPD 中 Tregs 的影响尚未完全了解。本研究旨在探讨 MDSCs 的免疫调节作用及其对 COPD 患者 Tregs 扩增和功能的潜在影响。
方法
采集外周血样本分析循环 MDSCs、Tregs、PD-1/PD-L1 表达，以评估 MDSC 的免疫调节作用及其对 COPD 中 Treg 扩增和功能的潜在影响。共纳入 54 例 COPD 患者和 24 例健康对照者。采用流式细胞术分析外周血中粒细胞 MDSCs（G-MDSCs）、单核细胞 MDSCs（M-MDSCs）、Tregs 以及 MDSCs 和 Tregs 上 PD-1/PD-L1（L2）的表达。
结果
与健康对照组相比，COPD 患者的 G-MDSCs 和 M-MDSCs 比例明显更高（ < 0.001）。此外，COPD 患者外周血 Tregs 的比例也明显更高。此外，在 COPD 患者中还检测到 Tregs 上细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）的表达增加（ < 0.01）。与对照组相比，COPD 患者 CD4T 细胞和 Tregs 上 PD-1 的表达增加，但 CD8T 细胞上 PD-1 的表达未增加。此外，在 COPD 患者中还观察到 M-MDSCs 上 PD-L1 的表达升高（ < 0.01）。在 COPD 患者中观察到 M-MDSCs 与 Tregs 的累积呈正相关。此外，循环 M-MDSCs 的百分比与 COPD 患者 Tregs 上 PD-1（r = 0.51， < 0.0001）和 CTLA-4（r = 0.42， = 0.0014）的水平呈正相关。
结论
在 COPD 中，MDSCs 的募集、Tregs 的累积以及 Tregs 上 CTLA-4 的上调，伴随着 PD-1/PD-L1 水平的升高，提示 PD-1/PD-L1 轴至少部分可能参与了 MDSCs 诱导的 Treg 扩增和激活。
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