{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:10:33Z","timestamp":1790266233418,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK09907"],"award-info":[{"award-number":["R01DK09907"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","award":["IISR-2014-1000892"],"award-info":[{"award-number":["IISR-2014-1000892"]}],"id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pfizer-ASPIRE Award","award":["WI227247"],"award-info":[{"award-number":["WI227247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izaa085","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T08:55:53Z","timestamp":1587804953000},"page":"797-808","source":"Crossref","is-referenced-by-count":152,"title":["Expression of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in the Gut of Patients With IBD"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7641-5136","authenticated-orcid":false,"given":"Juan F","family":"Burgue\u00f1o","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Reich","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, The Scripps Research Institute-Florida , Jupiter, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajar","family":"Hazime","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A","family":"Quintero","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Fritsch","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Santander","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivis","family":"Brito","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana M","family":"Damas","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Kerman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Gao","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"Ban","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Wang","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Pignac-Kobinger","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T","family":"Abreu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,25]]},"reference":[{"key":"2023112513153783200_CIT0001","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S0140-6736(20)30185-9","article-title":"A novel coronavirus outbreak of global health concern","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet."},{"key":"2023112513153783200_CIT0002","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N Engl J Med."},{"key":"2023112513153783200_CIT0003","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","author":"Guan","year":"2020","journal-title":"N Engl J Med."},{"key":"2023112513153783200_CIT0004","volume-title":"Coronavirus disease 2019 (COVID-19) Situation Report- 74","author":"WHO","year":"2020"},{"key":"2023112513153783200_CIT0005","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet."},{"key":"2023112513153783200_CIT0006","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature."},{"key":"2023112513153783200_CIT0007","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science."},{"key":"2023112513153783200_CIT0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","author":"Hoffmann","year":"2020;181:271\u2013280","journal-title":"Cell"},{"key":"2023112513153783200_CIT0009","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1128\/JVI.02232-10","article-title":"Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response","volume":"85","author":"Glowacka","year":"2011","journal-title":"J Virol."},{"key":"2023112513153783200_CIT0010","doi-asserted-by":"crossref","DOI":"10.1007\/s11684-020-0754-0","article-title":"Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection","author":"Zou","year":"2020","journal-title":"Front Med."},{"key":"2023112513153783200_CIT0011","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2020.03.044","article-title":"Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses","author":"Qi","year":"2020","journal-title":"Biochem Biophys Res Commun."},{"key":"2023112513153783200_CIT0012","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science."},{"key":"2023112513153783200_CIT0013","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.gastro.2003.08.001","article-title":"Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection","volume":"125","author":"Leung","year":"2003","journal-title":"Gastroenterology."},{"key":"2023112513153783200_CIT0014","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2020.02.055","article-title":"Evidence for gastrointestinal infection of SARS-CoV-2","author":"Xiao","year":"2020","journal-title":"Gastroenterology."},{"key":"2023112513153783200_CIT0015","doi-asserted-by":"crossref","DOI":"10.1038\/s41575-020-0295-7","article-title":"COVID-19: faecal-oral transmission?","author":"Hindson","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2023112513153783200_CIT0016","doi-asserted-by":"crossref","DOI":"10.1001\/jama.2020.3786","article-title":"Detection of SARS-CoV-2 in different types of clinical specimens","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"2023112513153783200_CIT0017","doi-asserted-by":"crossref","DOI":"10.1038\/s41591-020-0817-4","article-title":"Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding","author":"Xu","year":"2020; 26:502\u2013505","journal-title":"Nature Med."},{"key":"2023112513153783200_CIT0018","doi-asserted-by":"crossref","DOI":"10.1111\/jgh.15047","article-title":"Covid-19 and the digestive system","author":"Wong","year":"2020","journal-title":"J Gastroenterol Hepatol."},{"key":"2023112513153783200_CIT0019","first-page":"63","article-title":"Assessment of latent infections in patients receiving biological therapies","volume":"32 Suppl 2","author":"Fern\u00e1ndez-Ruiz","year":"2019","journal-title":"Rev Esp Quimioter."},{"key":"2023112513153783200_CIT0020","article-title":"The definition and risks of cytokine release syndrome-like in 11 COVID-19-infected pneumonia critically ill patients: disease characteristics and retrospective analysis","author":"Wang","year":"2020","journal-title":"medRxiv"},{"key":"2023112513153783200_CIT0021","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.3389\/fphys.2019.01484","article-title":"Intestinal epithelial cells respond to chronic inflammation and dysbiosis by synthesizing H2O2","volume":"10","author":"Burgue\u00f1o","year":"2019","journal-title":"Front Physiol."},{"key":"2023112513153783200_CIT0022","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12974-016-0653-0","article-title":"TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide","volume":"13","author":"Burgue\u00f1o","year":"2016","journal-title":"J Neuroinflammation."},{"key":"2023112513153783200_CIT0023","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1016\/j.celrep.2017.11.101","article-title":"STING-dependent signaling underlies IL-10 controlled inflammatory colitis","volume":"21","author":"Ahn","year":"2017","journal-title":"Cell Rep."},{"key":"2023112513153783200_CIT0024","doi-asserted-by":"crossref","first-page":"e2002417","DOI":"10.1371\/journal.pbio.2002417","article-title":"The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile","volume":"16","author":"Lyons","year":"2018","journal-title":"PLoS Biol."},{"key":"2023112513153783200_CIT0025","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1097\/MIB.0000000000000535","article-title":"Strong upregulation of AIM2 and IFI16 inflammasomes in the mucosa of patients with active inflammatory bowel disease","volume":"21","author":"Vanhove","year":"2015","journal-title":"Inflamm Bowel Dis."},{"key":"2023112513153783200_CIT0026","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1136\/gutjnl-2016-312609","article-title":"Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis","volume":"66","author":"Dotti","year":"2017","journal-title":"Gut."},{"key":"2023112513153783200_CIT0027","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics."},{"key":"2023112513153783200_CIT0028","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics."},{"key":"2023112513153783200_CIT0029","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics."},{"key":"2023112513153783200_CIT0030","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2023112513153783200_CIT0031","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J Pathol."},{"key":"2023112513153783200_CIT0032","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.stem.2016.04.003","article-title":"A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis","volume":"18","author":"Fujii","year":"2016","journal-title":"Cell Stem Cell."},{"key":"2023112513153783200_CIT0033","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00535-018-1437-3","article-title":"Single cell analysis of Crohn\u2019s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties","volume":"53","author":"Suzuki","year":"2018","journal-title":"J Gastroenterol."},{"key":"2023112513153783200_CIT0034","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/stem.1655","article-title":"Adult stem cells in the small intestine are intrinsically programmed with their location-specific function","volume":"32","author":"Middendorp","year":"2014","journal-title":"Stem Cells."},{"key":"2023112513153783200_CIT0035","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1136\/gutjnl-2017-314817","article-title":"DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development","volume":"68","author":"Kraiczy","year":"2019","journal-title":"Gut."},{"key":"2023112513153783200_CIT0036","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jcmgh.2019.10.013","article-title":"Microbial signatures and innate immune gene expression in lamina propria phagocytes of inflammatory bowel disease patients","volume":"9","author":"Dheer","year":"2020","journal-title":"Cell Mol Gastroenterol Hepatol."},{"key":"2023112513153783200_CIT0037","article-title":"Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients","author":"Zheng","year":"2020","journal-title":"Cell Mol Immunol."},{"key":"2023112513153783200_CIT0038","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/jlb.52.6.670","article-title":"Phosphatidylinositol hydrolysis by phospholipase A2 and C activities in human peripheral blood neutrophils","volume":"52","author":"Smith","year":"1992","journal-title":"J Leukoc Biol."},{"key":"2023112513153783200_CIT0039","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.virol.2006.06.011","article-title":"Interferon-gamma and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells","volume":"353","author":"de Lang","year":"2006","journal-title":"Virology."},{"key":"2023112513153783200_CIT0040","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41368-020-0074-x","article-title":"High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa","volume":"12","author":"Xu","year":"2020","journal-title":"Int J Oral Sci."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/6\/797\/5825063","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/6\/797\/5825063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T13:16:18Z","timestamp":1700918178000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/6\/797\/5825063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,25]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,4,25]]},"published-print":{"date-parts":[[2020,5,12]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izaa085","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6]]},"published":{"date-parts":[[2020,4,25]]}}}