Immune Landscape Changes in MASLD and the Effects of 11β-HSD1 Inhibition Revealed by Single-Cell Mass Cytometry.

IF 2.5 4区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

PROTEOMICS – Clinical Applications Pub Date : 2025-09-01 Epub Date: 2025-08-31 DOI:10.1002/prca.70022

Zayakhuu Gerelkhuu, Sehee Park, Yun Kim, Sang Won Lee, Dae Won Jun, Tae Hyun Yoon

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引用次数: 0

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly one-fourth of the global population, yet effective diagnostics and treatments remain limited. Systemic immune dysregulation plays a key role in MASLD pathogenesis, highlighting the value of immune profiling.

Methods: In this study, we used high-dimensional single-cell mass cytometry (CyTOF) to analyze peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 6), MASLD patients (n = 4), and MASLD patients treated with an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor (n = 2). PBMCs were stained with a 29-marker panel to identify 15 immune cell types and assess cytokine expression.

Results: MASLD patients showed increased CD8⁺ T cells, early NK cells, and monocytes, along with reductions in T_H2, T_H1, late NK, and Treg cells. Cytokine profiling revealed elevated IL-6 expression in plasmacytoid dendritic cells and late NK cells, indicating systemic inflammation. Automated clustering (PhenoGraph, UMAP) identified NK and phagocytic subsets associated with disease and treatment. Notably, 11β-HSD1 inhibition led to downregulation of pro-inflammatory cytokines (e.g., IFN-γ, IL-6) and partial restoration of immune subsets.

Conclusions: These results offer a high-resolution view of immune alterations in MASLD and suggest that 11β-HSD1 inhibition may represent a promising immunomodulatory therapeutic strategy.

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单细胞细胞计数法揭示MASLD免疫景观变化及11β-HSD1抑制作用

背景：代谢功能障碍相关的脂肪变性肝病（MASLD）影响了全球近四分之一的人口，但有效的诊断和治疗仍然有限。系统性免疫失调在MASLD发病机制中起关键作用，突出了免疫谱分析的价值。方法：在本研究中，我们使用高维单细胞大量细胞术（CyTOF）分析了健康供者（n = 6）、MASLD患者（n = 4）和接受11β-羟基类固醇脱氢酶1型（11β-HSD1）抑制剂治疗的MASLD患者（n = 2）的外周血单个核细胞（PBMCs）。用29个标记物对pbmc进行染色，以鉴定15种免疫细胞类型并评估细胞因子的表达。结果：MASLD患者CD8 + T细胞、早期NK细胞和单核细胞增加，TH2、TH1、晚期NK细胞和Treg细胞减少。细胞因子分析显示，浆细胞样树突状细胞和晚期NK细胞中IL-6表达升高，表明全身性炎症。自动聚类（表型图，UMAP）识别与疾病和治疗相关的NK和吞噬亚群。值得注意的是，11β-HSD1抑制导致促炎细胞因子（如IFN-γ， IL-6）的下调和免疫亚群的部分恢复。结论：这些结果提供了MASLD免疫改变的高分辨率视图，并表明11β-HSD1抑制可能是一种有前途的免疫调节治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PROTEOMICS – Clinical Applications 医学-生化研究方法

CiteScore

5.20

自引率

5.00%

发文量

审稿时长

1 months

期刊介绍： PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.