{"title":"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。","authors":"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","doi":"10.4168/aair.2024.16.1.55","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>Induced-sputum cells from newly physician-diagnosed EA, EB patients, and healthy controls (HCs) were collected for RNA sequencing.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"16 1","pages":"55-70"},"PeriodicalIF":4.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823142/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.\",\"authors\":\"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\",\"doi\":\"10.4168/aair.2024.16.1.55\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>Induced-sputum cells from newly physician-diagnosed EA, EB patients, and healthy controls (HCs) were collected for RNA sequencing.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":7547,\"journal\":{\"name\":\"Allergy, Asthma & Immunology Research\",\"volume\":\"16 1\",\"pages\":\"55-70\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823142/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Allergy, Asthma & Immunology Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4168/aair.2024.16.1.55\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy, Asthma & Immunology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4168/aair.2024.16.1.55","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.
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.
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.
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