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However, the dynamics and accurate derivation of Nrg1 expression during colitis remain unclear. By analyzing the public single-cell RNA-sequencing datasets and employing a dextran sulfate sodium (DSS)-induced colitis model, we investigated the cell source of Nrg1 expression and its potential regulator in the process of epithelial healing. Nrg1 was majorly expressed in stem-like fibroblasts arising early in mouse colon after DSS administration, and Nrg1\u2013Erbb3 signaling was identified as a potential mediator of interaction between stem-like fibroblasts and colonic epithelial cells. During the ongoing colitis phase, a significant infiltration of macrophages and neutrophils secreting IL-1\u03b2 emerged, accompanied by the rise in stem-like fibroblasts that co-expressed Nrg1 and IL-1 receptor 1. By stimulating intestinal or lung fibroblasts with IL-1\u03b2 in the context of inflammation, we observed a downregulation of Nrg1 expression. Patients with inflammatory bowel disease also exhibited an increase in NRG1+IL1R1+ fibroblasts and an interaction of NRG1\u2013ERBB between IL1R1+ fibroblasts and colonic epithelial cells. This study reveals a novel potential mechanism for mucosal healing after inflammation-induced epithelial injury, in which inflammatory myeloid cell-derived IL-1\u03b2 suppresses the early regeneration of intestinal tissue by interfering with the secretion of reparative neuregulin-1 by stem-like fibroblasts.<\/jats:p>","DOI":"10.3390\/ijms25084469","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T12:15:32Z","timestamp":1713442532000},"page":"4469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Myeloid Cell-Derived IL-1 Signaling Damps Neuregulin-1 from Fibroblasts to Suppress Colitis-Induced Early Repair of the Intestinal Epithelium"],"prefix":"10.3390","volume":"25","author":[{"given":"Ding","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhong Shan Er Lu, Guangzhou 510080, China"},{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoting","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaile","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-0688","authenticated-orcid":false,"given":"Ce","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhong Shan Er Lu, Guangzhou 510080, China"},{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Animal Experiment Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S2468-1253(23)00313-8","article-title":"Acute Severe Ulcerative Colitis Management: Unanswered Questions and Latest Insights","volume":"9","author":"Chaparro","year":"2024","journal-title":"Lancet Gastroenterol. 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