دورية أكاديمية
Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.
العنوان: | Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity. |
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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.) |
References: | Sci Rep. 2020 Sep 8;10(1):14639. (PMID: 32901054) PLoS Pathog. 2019 Jul 22;15(7):e1007940. (PMID: 31329638) Nat Cell Biol. 2020 Aug;22(8):919-926. (PMID: 32690888) Blood. 2008 Nov 15;112(10):4028-38. (PMID: 18799728) Nature. 2017 May 11;545(7653):238-242. (PMID: 28467820) Bioinformatics. 2016 Oct 1;32(19):3047-8. (PMID: 27312411) Cell Host Microbe. 2018 Nov 14;24(5):665-676.e4. (PMID: 30392829) Annu Rev Immunol. 2001;19:623-55. (PMID: 11244049) Science. 2013 Mar 22;339(6126):1441-5. (PMID: 23371553) Genes Chromosomes Cancer. 2012 Apr;51(4):353-74. (PMID: 22161874) Annu Rev Immunol. 2014;32:513-45. (PMID: 24555472) Cell. 1989 Aug 25;58(4):729-39. (PMID: 2475256) Nat Rev Immunol. 2008 Jul;8(7):559-68. (PMID: 18575461) Bioinformatics. 2012 Aug 15;28(16):2184-5. (PMID: 22743226) Science. 2015 Jan 16;347(6219):269-73. (PMID: 25431489) Nature. 2019 Oct;574(7777):249-253. (PMID: 31578523) J Virol. 2017 Mar 13;91(7):. (PMID: 28077655) Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677) Immunity. 2017 Mar 21;46(3):379-392. (PMID: 28329704) Science. 2023 Oct 27;382(6669):451-458. (PMID: 37883554) EMBO J. 2014 Apr 1;33(7):702-18. (PMID: 24562386) Science. 2014 Jan 3;343(6166):84-87. (PMID: 24336571) Nat Rev Gastroenterol Hepatol. 2021 Jan;18(1):7-23. (PMID: 33024279) Immunity. 2019 Sep 17;51(3):451-464.e6. (PMID: 31471108) Nat Genet. 2006 Nov;38(11):1335-40. (PMID: 17041601) Cell Signal. 2015 Jul;27(7):1509-16. (PMID: 25784454) Genome Biol. 2014;15(12):550. (PMID: 25516281) Nat Protoc. 2013 Dec;8(12):2471-82. (PMID: 24232249) Sci Adv. 2023 Nov 24;9(47):eadh9673. (PMID: 38000028) Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6. (PMID: 23203888) Cell Cycle. 2008 Jul 1;7(13):1925-30. (PMID: 18604160) Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):503-10. (PMID: 17702640) Cell. 2021 Jun 24;184(13):3573-3587.e29. (PMID: 34062119) Cell Mol Gastroenterol Hepatol. 2022;13(4):1223-1242. (PMID: 34952201) Science. 2020 Jan 24;367(6476):405-411. (PMID: 31974247) J Immunol. 2002 Aug 1;169(3):1261-9. (PMID: 12133947) J Interferon Cytokine Res. 2016 Jul;36(7):462-9. (PMID: 27379868) Front Cell Dev Biol. 2020 Sep 29;8:583115. (PMID: 33117810) Genome Biol. 2014;15(12):554. (PMID: 25476604) Nat Protoc. 2019 Mar;14(3):756-780. (PMID: 30710114) Nature. 2023 Apr;616(7955):152-158. (PMID: 36991121) J Virol. 2010 Jun;84(11):5670-7. (PMID: 20335250) J Virol. 2020 Oct 14;94(21):. (PMID: 32847859) PLoS Pathog. 2018 Nov 28;14(11):e1007420. (PMID: 30485383) Nature. 2012 Oct 4;490(7418):107-11. (PMID: 22902502) Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886) PLoS Pathog. 2015 Apr 07;11(4):e1004782. (PMID: 25849543) Nat Biotechnol. 2019 Mar;37(3):224-226. (PMID: 30809026) PLoS Pathog. 2008 Mar 14;4(3):e1000017. (PMID: 18369468) Dev Dyn. 2017 Sep;246(9):670-681. (PMID: 28643456) Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13710-5. (PMID: 21807998) Annu Rev Virol. 2019 Sep 29;6(1):567-584. (PMID: 31283436) Proc Natl Acad Sci U S A. 2011 May 10;108(19):7944-9. (PMID: 21518880) Sci Adv. 2023 Jul 14;9(28):eadg4055. (PMID: 37436979) Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):379-91. (PMID: 12220551) Elife. 2022 Feb 09;11:. (PMID: 35137688) Nat Genet. 2017 Feb;49(2):256-261. (PMID: 28067908) EMBO J. 2011 Nov 16;30(22):4571-85. (PMID: 21909072) Cell Rep. 2018 Dec 4;25(10):2784-2796.e3. (PMID: 30517866) Immunity. 2017 Apr 18;46(4):649-659. (PMID: 28410991) Virology. 2024 Jan;589:109921. (PMID: 37939648) J Biol Chem. 2014 Nov 7;289(45):31077-87. (PMID: 25246526) Cold Spring Harb Perspect Biol. 2018 Nov 1;10(11):. (PMID: 28963109) |
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 |
تدمد: | 1935-3456 |
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DOI: | 10.1016/j.mucimm.2024.03.013 |