{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:48:09Z","timestamp":1792097289507,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Molecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage\u2010associated diagnostic signature for CRSwNP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010Expression 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\u2010cell RNA sequencing data. Immunofluorescence co\u2010staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow\u2010derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four\u2010gene 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Single\u2010cell 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163\u00a0+\u00a0HMOX1\u00a0+\u00a0M2 macrophages in mouse BMDM cultures (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05 respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>M2 macrophage\u2010derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clt2.70014","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T12:48:48Z","timestamp":1733575728000},"source":"Crossref","is-referenced-by-count":11,"title":["M2 macrophage derived HMOX1 defines chronic rhinosinusitis with nasal polyps"],"prefix":"10.1002","volume":"14","author":[{"given":"Enhao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghe","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Otolaryngology Beijing Laboratory of Allergic Diseases Beijing Key Laboratory of Nasal Diseases Key Laboratory of Otolaryngology Head and Neck Surgery Ministry of Education Capital Medical University  Beijing China"},{"name":"Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences  Beijing 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