Stefanie Westermann, Daniel Radtke, Lisa Kramer, Stefan Wirtz, David Voehringer
{"title":"Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.","authors":"Stefanie Westermann, Daniel Radtke, Lisa Kramer, Stefan Wirtz, David Voehringer","doi":"10.1002/eji.202451394","DOIUrl":null,"url":null,"abstract":"<p><p>Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports hint at a role for signal transducer and activator of transcription (STAT) 6 signaling in non-immune cells, the contribution of STAT6-activation particularly in intestinal epithelial cells (IECs) is still unknown. Dextran sodium sulfate (DSS)-induced colitis is a model for UC in mice that we applied here on animals with expression of a constitutively active version of STAT6 in IECs (VillinCre_STAT6vt mice). We report increased pathology and mortality due to enhanced and systemic inflammation in these mice. Bulk RNA sequencing of colonic tissue from naïve VillinCre_STAT6vt mice showed differential expression of more than 140 genes compared to control mice. Gene set enrichment analysis revealed STAT6-regulated expression of the unfolded protein response, MTORC- and MYC-signaling, and protein secretion pathways. A comparison of gene expression in the colon of naïve VillinCre_STAT6vt mice and a human single-cell RNA sequencing dataset of a patient cohort with IBD revealed overlapping changes in the epithelial and macrophage compartment compared to corresponding controls. In conclusion, we found that activation of STAT6 in the intestinal epithelium predisposes to exacerbated colitis and gut inflammation.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451394"},"PeriodicalIF":4.5000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/eji.202451394","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports hint at a role for signal transducer and activator of transcription (STAT) 6 signaling in non-immune cells, the contribution of STAT6-activation particularly in intestinal epithelial cells (IECs) is still unknown. Dextran sodium sulfate (DSS)-induced colitis is a model for UC in mice that we applied here on animals with expression of a constitutively active version of STAT6 in IECs (VillinCre_STAT6vt mice). We report increased pathology and mortality due to enhanced and systemic inflammation in these mice. Bulk RNA sequencing of colonic tissue from naïve VillinCre_STAT6vt mice showed differential expression of more than 140 genes compared to control mice. Gene set enrichment analysis revealed STAT6-regulated expression of the unfolded protein response, MTORC- and MYC-signaling, and protein secretion pathways. A comparison of gene expression in the colon of naïve VillinCre_STAT6vt mice and a human single-cell RNA sequencing dataset of a patient cohort with IBD revealed overlapping changes in the epithelial and macrophage compartment compared to corresponding controls. In conclusion, we found that activation of STAT6 in the intestinal epithelium predisposes to exacerbated colitis and gut inflammation.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.