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自身免疫性肝炎患者外周血单个核细胞的特征及潜在相关分子机制:单细胞 RNA 测序分析。

Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.

机构信息

Department of Gastroenterology, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.

出版信息

Med Mol Morphol. 2024 Jun;57(2):110-123. doi: 10.1007/s00795-024-00380-5. Epub 2024 Feb 10.

Abstract

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.

摘要

自身免疫性肝炎(AIH)是一种免疫失调疾病,其特征为高γ球蛋白血症、自身抗体和肝组织学上的慢性活动性肝炎。然而,AIH 患者的免疫细胞群体特征仍知之甚少。本研究旨在通过单细胞 RNA 测序(scRNA-seq)分析 AIH 患者外周血单个核细胞(PBMC)的特征,并探讨潜在的 AIH 相关分子机制。我们通过 scRNA-seq 分别生成了 4 名健康对照(HC)和 4 名 AIH 患者 PBMC 混合样本的 3690 个和 3511 个单细胞转录组。这些混合 PBMC 转录组用于细胞簇识别和差异表达基因(DEG)识别。对 DEGs 进行 GO 功能富集分析,以确定最活跃的 AIH 免疫细胞生物学功能。尽管基于 PCA 的统一流形逼近和投影(UMAP)算法用于聚类两个样本中具有相似表达模式的细胞,但在 AIH PBMC 中的单核细胞中保留了 87 个上调和 12 个下调的 DEG,在 NK 细胞中保留了 101 个上调和 15 个下调的 DEG。此外,在 PBMC 衍生的单核细胞和 NK 细胞簇中富集的 GO 术语主要与抗原加工和呈递、IFN-γ 介导的信号转导以及中性粒细胞脱颗粒和活化有关。这些潜在的分子机制可能是 AIH 治疗的重要靶点。

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