Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.

IF 4.1 2区医学 Q2 ALLERGY

Allergy, Asthma & Immunology Research Pub Date : 2024-01-01 DOI:10.4168/aair.2024.16.1.55

Wenzhi Zhan, Wei Luo, Yulong Zhang, Keheng Xiang, Xiaomei Chen, Shuirong Shen, Chuqing Huang, Tingting Xu, Wenbin Ding, Yuehan Chen, Mingtong Lin, Xinghua Pan, Kefang Lai

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Abstract

Purpose: Eosinophilic asthma (EA) and non-asthmatic eosinophilic bronchitis (EB) share similar eosinophilic airway inflammation. Unlike EA, EB did not present airway hyperresponsiveness or airflow obstruction. We aimed to compare the mechanism underlying the different manifestations between EA and EB via sputum transcriptomics analysis.

Methods: Induced-sputum cells from newly physician-diagnosed EA, EB patients, and healthy controls (HCs) were collected for RNA sequencing.

Results: Bulk RNA sequencing was performed using sputum cells from patients with EA (n = 18), EB (n = 15) and HCs (n = 28). Principal component analysis revealed similar gene expression patterns in EA and EB. The most differentially expressed genes in EB compared with HC were also shared by EA, including IL4, IL5 IL13, CLC, CPA3, and DNASE1L3. However, gene set enrichment analysis showed that the signatures regulating macrophage activation were enriched in EA compared to EB. Sputum cells were profiled using single-cell RNA sequencing. FABP4+ macrophages, SPP1+ macrophages, FCN1+ macrophages, dendritic cells, T cells, B cells, mast cells, and epithelial cells were identified based on gene expression profiling. Analysis of cell-cell communication revealed that interactions between FCN1+ macrophages and other cells were higher in EA than in EB. A wealth of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) interactions between FCN1+ macrophages and other cells have been shown in EA. The gene expression levels of EREG, TGFBI, and VEGFA in FCN1+ macrophages of EA were significantly higher than those of EB. Furthermore, signatures associated with the response to TGF-β, cellular response to VEGF stimulus and developmental cell growth were enriched in FCN1+ macrophages of EA compared to those of EB.

Conclusions: FCN1+ macrophage activation associated with airway remodeling processes was upregulated in EA compared to that in EB, which may contribute to airway hyperresponsiveness and airflow obstruction.

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与非嗜酸性粒细胞性支气管炎相比，痰转录组学揭示了轻度嗜酸性粒细胞性哮喘中FCN1+巨噬细胞的活化。

目的：嗜酸性粒细胞性哮喘（EA）和非哮喘性嗜酸性粒细胞支气管炎（EB）具有相似的嗜酸性粒细胞气道炎症。与 EA 不同的是，EB 不会出现气道高反应性或气流阻塞。我们的目的是通过痰转录组学分析比较 EA 和 EB 不同表现的机制：方法：收集新近被医生诊断为EA、EB患者和健康对照组（HCs）的诱导痰细胞进行RNA测序：利用EA（18人）、EB（15人）和HC（28人）患者的痰细胞进行了大量RNA测序。主成分分析显示，EA和EB的基因表达模式相似。与HC相比，EB中差异表达最大的基因也与EA相同，包括IL4、IL5、IL13、CLC、CPA3和DNASE1L3。然而，基因组富集分析表明，与EB相比，调节巨噬细胞活化的特征在EA中更为富集。使用单细胞 RNA 测序分析了痰细胞。根据基因表达谱分析，确定了FABP4+巨噬细胞、SPP1+巨噬细胞、FCN1+巨噬细胞、树突状细胞、T细胞、B细胞、肥大细胞和上皮细胞。对细胞间通讯的分析表明，EA 中 FCN1+ 巨噬细胞与其他细胞间的相互作用高于 EB。在EA中，FCN1+巨噬细胞与其他细胞之间存在大量转化生长因子β（TGF-β）和血管内皮生长因子（VEGF）的相互作用。EA FCN1+ 巨噬细胞中 EREG、TGFBI 和 VEGFA 的基因表达水平明显高于 EB。此外，与EB相比，EA的FCN1+巨噬细胞中与TGF-β反应、细胞对VEGF刺激的反应和细胞生长发育相关的特征更为丰富：结论：与EB相比，EA中与气道重塑过程相关的FCN1+巨噬细胞激活被上调，这可能会导致气道高反应性和气流阻塞。

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

Allergy, Asthma & Immunology Research ALLERGY-IMMUNOLOGY

CiteScore

6.10

自引率

6.80%

发文量

审稿时长

>12 weeks

期刊介绍： The journal features cutting-edge original research, brief communications, and state-of-the-art reviews in the specialties of allergy, asthma, and immunology, including clinical and experimental studies and instructive case reports. Contemporary reviews summarize information on topics for researchers and physicians in the fields of allergy and immunology. As of January 2017, AAIR do not accept case reports. However, if it is a clinically important case, authors can submit it in the form of letter to the Editor. Editorials and letters to the Editor explore controversial issues and encourage further discussion among physicians dealing with allergy, immunology, pediatric respirology, and related medical fields. AAIR also features topics in practice and management and recent advances in equipment and techniques for clinicians concerned with clinical manifestations of allergies and pediatric respiratory diseases.