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单细胞分辨率下儿童脓毒症免疫失调的全貌

The landscape of immune dysregulation in pediatric sepsis at a single-cell resolution.

作者信息

Alhamdan Fahd, Koutsogiannaki Sophia, Yuki Koichi

机构信息

Department of Anesthesiology, Critical Care, and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, USA; Department of Immunology and Anaesthesia, Harvard Medical School, USA; Broad Institute of MIT and Harvard, USA.

Department of Anesthesiology, Critical Care, and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, USA; Department of Immunology and Anaesthesia, Harvard Medical School, USA; Broad Institute of MIT and Harvard, USA.

出版信息

Clin Immunol. 2024 May;262:110175. doi: 10.1016/j.clim.2024.110175. Epub 2024 Mar 7.

Abstract

Recognizing immune dysregulation as a hallmark of sepsis pathophysiology, leukocytes have attracted major attention of investigation. While adult and pediatric sepsis are clinically distinct, their immunological delineation remains limited. Single cell technologies facilitated the characterization of immune signatures. We tackled to delineate immunological profiles of pediatric sepsis at a single-cell level by analyzing blood samples from six septic children, at both acute and recovery phases, and four healthy children. 16 single-cell transcriptomic datasets were analyzed and compared to adult sepsis dataset. We showed a unique shift in neutrophil subpopulations and functions between acute and recovery phases, along with the regulatory role of resistin. Neutrophil signatures were comparable between adult and pediatric sepsis. Innate-like CD4 T cells were predominantly and uniquely observed in acute phase of pediatric sepsis. Our study serves as a rich source of information about the phenotypic diversity and trajectory of circulating immune cells during pediatric sepsis.

摘要

鉴于免疫失调是脓毒症病理生理学的一个标志,白细胞已成为主要的研究对象。虽然成人和儿童脓毒症在临床上有所不同,但其免疫学特征仍不明确。单细胞技术有助于免疫特征的表征。我们通过分析六名脓毒症儿童在急性期和恢复期的血样以及四名健康儿童的血样,在单细胞水平上描绘儿童脓毒症的免疫图谱。分析了16个单细胞转录组数据集,并与成人脓毒症数据集进行比较。我们发现中性粒细胞亚群和功能在急性期和恢复期之间发生了独特的变化,同时抵抗素也发挥了调节作用。成人和儿童脓毒症的中性粒细胞特征具有可比性。在儿童脓毒症急性期主要且独特地观察到了固有样CD4 T细胞。我们的研究为了解儿童脓毒症期间循环免疫细胞的表型多样性和轨迹提供了丰富的信息来源。

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