دورية أكاديمية
أعرض في EDS

Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.

التفاصيل البيبلوغرافية
العنوان: Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.
المؤلفون: Wright AP; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Harris S; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Madden S; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Reyes BR; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Mulamula E; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Gibson A; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Rauch I; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Constant DA; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA., Nice TJ; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA. Electronic address: nice@ohsu.edu.
المصدر: Mucosal immunology [Mucosal Immunol] 2024 Aug; Vol. 17 (4), pp. 633-650. Date of Electronic Publication: 2024 Apr 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 101299742 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1935-3456 (Electronic) Linking ISSN: 19330219 NLM ISO Abbreviation: Mucosal Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2023- : [New York, NY] : Elsevier
Original Publication: New York, NY : Nature Pub. Group, c2008-
مواضيع طبية MeSH: Interferon Regulatory Factors*/metabolism , Interferon Regulatory Factors*/genetics , Mice, Knockout* , Intestinal Mucosa*/immunology , Intestinal Mucosa*/metabolism , Epithelial Cells*/immunology , Epithelial Cells*/metabolism , Immunity, Innate* , Organoids*, Animals ; Mice ; Cell Differentiation ; Interferons/metabolism ; Mice, Inbred C57BL ; Gene Expression Regulation ; Inflammasomes/metabolism ; Macrophages/immunology ; Macrophages/metabolism
مستخلص: Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screens found that Irf6 deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages. Furthermore, knockout (KO) of Irf6 in IEC organoids resulted in profound changes to homeostasis and immunity gene expression. Irf6 KO organoids grew more slowly, and single-cell ribonucleic acid sequencing indicated reduced expression of genes in epithelial differentiation and immunity pathways. IFN-stimulated gene expression was also significantly different in Irf6 KO organoids, with increased expression of stress and apoptosis-associated genes. Functionally, the transcriptional changes in Irf6 KO organoids were associated with increased cytotoxicity upon IFN treatment or inflammasome activation. These data indicate a previously unappreciated role for IRF6 in IEC biology, including regulation of epithelial development and moderation of innate immune responses to minimize cytotoxicity and maintain barrier function.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 AI130055 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Interferon Regulatory Factors)
0 (IRF6 protein, mouse)
9008-11-1 (Interferons)
0 (Inflammasomes)
تواريخ الأحداث: Date Created: 20240411 Date Completed: 20240812 Latest Revision: 20240815
رمز التحديث: 20240815
مُعرف محوري في PubMed: PMC11323225
DOI: 10.1016/j.mucimm.2024.03.013
PMID: 38604478
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-3456
DOI:10.1016/j.mucimm.2024.03.013