Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers
{"title":"转录组学和eqtl揭示了乳糜泻十二指肠内膜的炎症异质性。","authors":"Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers","doi":"10.1038/s41435-025-00356-0","DOIUrl":null,"url":null,"abstract":"<p><p>In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.</p>","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.\",\"authors\":\"Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers\",\"doi\":\"10.1038/s41435-025-00356-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.</p>\",\"PeriodicalId\":12691,\"journal\":{\"name\":\"Genes and immunity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes and immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41435-025-00356-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes and immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41435-025-00356-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.
In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.
期刊介绍:
Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.