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单细胞 RNA 测序和免疫受体分析揭示了脓毒症患者外周血中与动态免疫相关的特征。

Single-cell RNA sequencing and immune repertoire analysis revealed dynamic immune characteristics associated with peripheral blood during sepsis.

机构信息

Academy of Military Medical Sciences, Beijing, 100850, China; Department of Morphology Laboratory, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, China.

Academy of Military Medical Sciences, Beijing, 100850, China.

出版信息

Biochem Biophys Res Commun. 2024 Nov 19;734:150751. doi: 10.1016/j.bbrc.2024.150751. Epub 2024 Sep 27.

DOI:10.1016/j.bbrc.2024.150751
PMID:39357334
Abstract

Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4 and CD8 T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis.

摘要

脓毒症是一种潜在的致命疾病,由感染引起的异常免疫反应导致,可能导致器官衰竭甚至死亡。为了探索脓毒症期间免疫反应失调的机制,并确定潜在的治疗靶点,我们进行了单细胞 RNA 测序(scRNA-seq)和免疫受体库分析,以描绘脓毒症小鼠外周血细胞的细胞景观。我们观察到脓毒症导致外周血细胞数量和比例发生显著变化。通过结合单细胞基因表达谱和 B 细胞受体(BCR)受体库分析,我们发现感染在短时间内严重损害了 B 细胞的抗原呈递能力和 BCR 的多样性。此外,我们发现小鼠的盲肠结扎和穿孔术抑制了 CD4 和 CD8 T 细胞的通讯信号,并减少了 B 细胞与其他细胞之间的相互作用。我们的研究提供了关于脓毒症驱动的外周血细胞生物学特性的动态变化的详细见解,并为我们理解脓毒症期间的免疫紊乱提供了重要进展。

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