Amy E. O’Connell , Sathuwarman Raveenthiraraj , Luiz Fernando Silva Oliveira , Comfort Adegboye , Venkata Siva Dasuri , Wanshu Qi , Radhika S. Khetani , Akaljot Singh , Nambirajam Sundaram , Jasmine Lin , Prathima Nandivada , Lorena Rincón-Cruz , Jeffrey D. Goldsmith , Jay R. Thiagarajah , Diana L. Carlone , Jerrold R. Turner , Pankaj B. Agrawal , Michael Helmrath , David T. Breault
{"title":"WNT2B 缺陷会导致炎性细胞因子分泌增加，从而增强对结肠炎的易感性。","authors":"Amy E. O’Connell , Sathuwarman Raveenthiraraj , Luiz Fernando Silva Oliveira , Comfort Adegboye , Venkata Siva Dasuri , Wanshu Qi , Radhika S. Khetani , Akaljot Singh , Nambirajam Sundaram , Jasmine Lin , Prathima Nandivada , Lorena Rincón-Cruz , Jeffrey D. Goldsmith , Jay R. Thiagarajah , Diana L. Carlone , Jerrold R. Turner , Pankaj B. Agrawal , Michael Helmrath , David T. Breault","doi":"10.1016/j.jcmgh.2024.04.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Background & aims</h3><p>Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.</p></div><div><h3>Methods</h3><p>We investigated the intestinal health of <em>Wnt2b</em> knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue.</p></div><div><h3>Results</h3><p>Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. <em>Wnt2b</em> KO mice showed an enhanced inflammatory signature after DSS treatment. <em>Wnt2b</em> KO colon and human WNT2B-deficient organoids had increased levels of <em>CXCR4</em> and <em>IL6</em>, and biopsy tissue from humans showed increased neutrophils.</p></div><div><h3>Conclusions</h3><p>WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 2","pages":"Article 101349"},"PeriodicalIF":7.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001000/pdfft?md5=aad7f8851649bbb9688db7c5a88219f4&pid=1-s2.0-S2352345X24001000-main.pdf","citationCount":"0","resultStr":"{\"title\":\"WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production\",\"authors\":\"Amy E. O’Connell , Sathuwarman Raveenthiraraj , Luiz Fernando Silva Oliveira , Comfort Adegboye , Venkata Siva Dasuri , Wanshu Qi , Radhika S. Khetani , Akaljot Singh , Nambirajam Sundaram , Jasmine Lin , Prathima Nandivada , Lorena Rincón-Cruz , Jeffrey D. Goldsmith , Jay R. Thiagarajah , Diana L. Carlone , Jerrold R. Turner , Pankaj B. Agrawal , Michael Helmrath , David T. Breault\",\"doi\":\"10.1016/j.jcmgh.2024.04.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background & aims</h3><p>Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.</p></div><div><h3>Methods</h3><p>We investigated the intestinal health of <em>Wnt2b</em> knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue.</p></div><div><h3>Results</h3><p>Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. <em>Wnt2b</em> KO mice showed an enhanced inflammatory signature after DSS treatment. <em>Wnt2b</em> KO colon and human WNT2B-deficient organoids had increased levels of <em>CXCR4</em> and <em>IL6</em>, and biopsy tissue from humans showed increased neutrophils.</p></div><div><h3>Conclusions</h3><p>WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.</p></div>\",\"PeriodicalId\":55974,\"journal\":{\"name\":\"Cellular and Molecular Gastroenterology and Hepatology\",\"volume\":\"18 2\",\"pages\":\"Article 101349\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2352345X24001000/pdfft?md5=aad7f8851649bbb9688db7c5a88219f4&pid=1-s2.0-S2352345X24001000-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular and Molecular Gastroenterology and Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2352345X24001000\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352345X24001000","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production
Background & aims
Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.
Methods
We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue.
Results
Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils.
Conclusions
WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.
期刊介绍：
"Cell and Molecular Gastroenterology and Hepatology (CMGH)" is a journal dedicated to advancing the understanding of digestive biology through impactful research that spans the spectrum of normal gastrointestinal, hepatic, and pancreatic functions, as well as their pathologies. The journal's mission is to publish high-quality, hypothesis-driven studies that offer mechanistic novelty and are methodologically robust, covering a wide range of themes in gastroenterology, hepatology, and pancreatology.
CMGH reports on the latest scientific advances in cell biology, immunology, physiology, microbiology, genetics, and neurobiology related to gastrointestinal, hepatobiliary, and pancreatic health and disease. The research published in CMGH is designed to address significant questions in the field, utilizing a variety of experimental approaches, including in vitro models, patient-derived tissues or cells, and animal models. This multifaceted approach enables the journal to contribute to both fundamental discoveries and their translation into clinical applications, ultimately aiming to improve patient care and treatment outcomes in digestive health.
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