M2 macrophage derived HMOX1 defines chronic rhinosinusitis with nasal polyps

IF 4.6 2区医学 Q2 ALLERGY Clinical and Translational Allergy Pub Date : 2024-12-07 DOI:10.1002/clt2.70014

Enhao Wang, Yanghe Hao, Jing Song, Jing Yuan, Yu Hong, Ying Li, Yang Wang, Chengshuo Wang, Ming Wang, Luo Zhang

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Abstract

Background

Molecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage-associated diagnostic signature for CRSwNP.

Methods

Transcriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co-Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single-cell RNA sequencing data. Immunofluorescence co-staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow-derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.

Results

DEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four-gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p < 0.001). Single-cell RNA sequencing data underscored the altered cellular composition in CRSwNP, with HMOX1 notably expressed in M2 macrophages. Immunofluorescence staining highlighted the increased infiltration of CD163+ M2 macrophages in nasal mucosa samples of eosinophilic CRSwNP, which correlated with HMOX1 protein levels (p < 0.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163 + HMOX1 + M2 macrophages in mouse BMDM cultures (p < 0.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26; p < 0.05 respectively).

Conclusion

M2 macrophage-derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.

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M2巨噬细胞衍生的HMOX1定义慢性鼻窦炎伴鼻息肉。

背景：慢性鼻窦炎伴鼻息肉（CRSwNP）与巨噬细胞相关的分子特征尚不清楚。本研究旨在开发巨噬细胞相关的CRSwNP诊断特征。方法：使用来自54例CRSwNP患者和37名健康对照者的转录组数据，通过GSE136825、GSE36830和GSE72713鉴定两组之间的差异表达基因（DEGs）。基因集富集分析和加权基因共表达网络分析确定了关键途径和基因簇。根据这些分析和受试者工作特征曲线（ROC）建立诊断模型，并在29个样本的转录组数据中进一步验证。进行免疫细胞浸润分析，将这些诊断基因与巨噬细胞联系起来，并通过单细胞RNA测序数据进行验证。对鼻组织进行CD163和HMOX1的免疫荧光共染色。小鼠骨髓源性巨噬细胞（bmdm）培养物用于功能实验。研究了HMOX1与eotaxin基因表达的相关性。结果：与对照组相比，CRSwNP的deg在白细胞介素_4_和_13_信号通路中富集。建立了四基因诊断模型（HMOX1、ALOX5、F13A1和ITGB2），训练集的ROC曲线下面积为0.980，测试集的ROC曲线下面积为0.895，诊断精度较高。结论：M2巨噬细胞衍生的HMOX1可作为CRSwNP的创新诊断标志，可能是嗜酸性炎症的潜在调节因子。

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

Clinical and Translational Allergy Immunology and Microbiology-Immunology

CiteScore

7.50

自引率

4.50%

发文量

117

审稿时长

12 weeks

期刊介绍： Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.