About: Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon

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About: Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon
Creator	Arnauts, Kaline Cleynen, Isabelle Ferrante, Marc Ke, Bo-Jun Matteoli, Gianluca Rahiman, Abdu Sabino, João Saeed, ; Séverine Vermeire, $ Vermeire, Séverine Verstockt, Bram Verstockt, Sare
source	BioRxiv
abstract	Patients with IBD are considered immunosuppressed, but do not seem more vulnerable for COVID-19. Nevertheless, intestinal inflammation has shown an important risk factor for SARS-CoV-2 infection and prognosis. Therefore, we investigated the effect of intestinal inflammation on the viral intestinal entry mechanisms, including ACE2, in IBD. We collected (un)inflamed mucosal biopsies from CD (n=193) and UC (n=158) patients, and 51 matched non-IBD controls for RNA sequencing, differential gene expression and co-expression analysis. Organoids from UC patients were subjected to an inflammatory mix and processed for RNA sequencing. Transmural ileal biopsies were processed for single-cell (sc) sequencing. Publicly available colonic sc-RNA sequencing data, and microarrays from tissue pre/post anti-TNF therapy, were analyzed. In inflamed CD ileum, ACE2 was significantly decreased compared to control ileum (p=4.6E-07), whereas colonic ACE2 expression was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). Sc-RNA sequencing confirmed this ACE2 dysregulation, and exclusive epithelial ACE2 expression. Network analyses highlighted HNF4A as key regulator of ileal ACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonic ACE2. Inflammatory stimuli upregulated ACE2 in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). Anti-TNF therapy restored colonic ACE2 dysregulation in responders. Intestinal inflammation alters SARS-CoV-2 coreceptors in the intestine, with opposing effects in ileum and colon. HNF4A, an IBD susceptibility gene, is an important upstream regulator of ACE2 in ileum, whereas interferon signaling dominates in colon. Our data support the importance of adequate control of IBD in order to reduce risk of (complicated) COVID-19.
has issue date	2020-06-24(xsd:dateTime)
bibo:doi	10.1101/2020.06.24.169383
has license	biorxiv
sha1sum (hex)	36d5e0b44efeca948893024442d42fc96dda821b
schema:url	https://doi.org/10.1101/2020.06.24.169383
resource representing a document's title	Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon
schema:publication	bioRxiv
resource representing a document's body	covid:36d5e0b44efeca948893024442d42fc96dda821b#body_text
is schema:about of	named entity 'inflammation' named entity 'interferon' named entity 'tissue' named entity 'ileum' named entity 'receptor' named entity 'IBD' named entity 'Nevertheless' named entity 'immunosuppressed' named entity 'IBD' named entity 'inflammation' named entity 'SARS-CoV-2' named entity 'HNF4A' named entity 'interferon' named entity 'expression of genes' named entity 'ACE2' named entity 'microbial' named entity 'lungs' named entity 'ACE2' named entity 'lysis buffer' named entity 'ileum' named entity 'IBD' named entity '37°C' named entity 'MERS' named entity 'prognosis' named entity 'DPP4' named entity 'TMPRSS2' named entity 'inflammation' named entity 'Illumina' named entity 'TMPRSS2' named entity 'diarrhea' named entity 'IBD' named entity 'ileal' named entity 'AE1/AE3' named entity 'RNA seq' named entity 'IFNγ' named entity 'collagenase' named entity 'deficient mice' named entity 'nausea' named entity 'SLC6A20' named entity 'TMPRSS2' named entity 'TNF-α' named entity 'enterocytes' named entity 'international registries' named entity 'COVID-19' named entity 'enterocytes' named entity 'chromium' named entity 'COVID-19 disease' named entity 'intestinal microbiome' named entity 'ACE2' named entity 'transcriptional' named entity 'IBD' named entity 'Belgium' named entity 'DPP4' named entity 'large intestine' named entity 'ACE2' named entity 'genotypes' named entity 'virus' named entity 'Qiagen' named entity 'ACE2' named entity 'colon' named entity 'ileum' named entity 'IBD' named entity 'ileal' named entity 'expressed genes' named entity 'ACE2' named entity 'ileum' named entity 'Quality control' named entity 'ACE2' named entity 'ACE2' named entity 'biopsies' named entity 'inflammation' named entity 'biopsies' named entity 'inflammation'

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