Single-cell analysis reveals dysregulated inflammatory response in peripheral blood immunity in patients with acute respiratory distress syndrome.
Single-cell analysis reveals dysregulated inflammatory response in peripheral blood immunity in patients with acute respiratory distress syndrome.
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DOI：
10.3389/fcell.2023.1199122
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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简介：急性呼吸窘迫综合征（ARDS）仍然是重症监护病房患者面临的主要临床挑战。确定不同病因的ARDS的差异机制是提高ARDS治疗效果的关键目标。尽管越来越多的证据表明不同的免疫细胞类型参与了ARDS，但免疫细胞亚群改变在疾病进展中的作用尚未阐明。 研究方法：在这项研究中，我们结合scRNA-seq和批量水平测序来分析健康志愿者和脓毒性ARDS（sep-ARDS）和肺炎性ARDS（PNE-ARDS）患者外周血单核细胞的转录组。 结果如下：我们的数据揭示了不同病因的ARDS在细胞和分子水平以及生物信号通路内的差异性改变。中性粒细胞、巨噬细胞（Macs）、经典树突状细胞（cDCs）、髓源性抑制细胞（MDSC）和CD 8 + T细胞的动态在不同样本组之间变化显著，在sep-ARDS患者中，中性粒细胞和cDCs的量较高，Macs的量显著较低。此外，MDSC仅在sep-ARDS患者中高度富集，而在PNE-ARDS患者中观察到更高丰度的CD 8 + T细胞。此外，发现这些细胞亚群显著参与细胞凋亡、炎症和免疫相关途径。特别是，在中性粒细胞亚群中观察到氧化应激反应的显著增强。 结论：我们的研究表明，参与主要外周循环的细胞组成在不同病因的ARDS患者中存在差异。研究这些细胞在ARDS中的作用和作用机制将为治疗这种疾病提供新的机会。
Introduction: Acute respiratory distress syndrome (ARDS) remains a major clinical challenge for patients in intensive care units. Determining the differential mechanisms underlying ARDS with different etiologies is a key goal to improve the effectiveness of ARDS therapy. Despite growing evidence that different immune cell types are involved in ARDS, the role of altered immune cell subpopulations in disease progression is unelucidated. Methods: In this study, we combined scRNA-seq and bulk-level sequencing to analyze the transcriptomes of peripheral blood mononuclear cells from healthy volunteers and patients with septic ARDS (sep-ARDS) and pneumonic ARDS (PNE-ARDS). Results: Our data revealed differential alterations at the cellular and molecular levels and within biological signaling pathways in ARDS with different etiologies. The dynamics of neutrophils, macrophages (Macs), classical dendritic cells (cDCs), myeloid-derived suppressive cells (MDSCs), and CD8+ T cells varied significantly among groups of different samples, with neutrophils and cDCs at higher, and Macs at significantly lower, amounts in the patients with sep-ARDS. Furthermore, MDSCs were highly enriched only in the sep-ARDS patients, whereas a higher abundance of CD8+ T cells was observed in patients with PNE-ARDS. In addition, these cell subpopulations were found to be significantly involved in apoptosis, inflammatory, and immune-related pathways. In particular, a significant enhancement of the oxidative stress response was observed in the neutrophil subpopulation. Conclusion: Our study shows that the composition of cells involved in the main peripheral circulation differs in patients with ARDS with different etiologies. Studying the role and mechanism of action of these cells during ARDS will provide new opportunities for the treatment of this condition.