دورية أكاديمية
أعرض في EDS

Agr2-associated ER stress promotes adherent-invasive E. coli dysbiosis and triggers CD103 + dendritic cell IL-23-dependent ileocolitis.

التفاصيل البيبلوغرافية
العنوان: Agr2-associated ER stress promotes adherent-invasive E. coli dysbiosis and triggers CD103 + dendritic cell IL-23-dependent ileocolitis.
المؤلفون: Viladomiu M; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Khounlotham M; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Dogan B; College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA., Lima SF; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Elsaadi A; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Cardakli E; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Castellanos JG; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA., Ng C; Department of Pathology, Weill Cornell Medicine, New York, NY 10021, USA., Herzog J; Departments of Medicine and Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Schoenborn AA; Department of Pediatrics, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Ellermann M; Departments of Medicine and Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Liu B; Departments of Medicine and Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Zhang S; College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA., Gulati AS; Department of Pediatrics, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Sartor RB; Departments of Medicine and Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Simpson KW; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA; College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA., Lipkin SM; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: stl2012@med.cornell.edu., Longman RS; Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA; Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: ral2006@med.cornell.edu.
المصدر: Cell reports [Cell Rep] 2022 Nov 15; Vol. 41 (7), pp. 111637.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Crohn Disease*/genetics , Crohn Disease*/microbiology , Dysbiosis* , Mucoproteins*/genetics , Escherichia coli Infections*, Animals ; Humans ; Mice ; Dendritic Cells ; Escherichia coli ; Interleukin-23 ; Oncogene Proteins
مستخلص: Endoplasmic reticulum (ER) stress is associated with Crohn's disease (CD), but its impact on host-microbe interaction in disease pathogenesis is not well defined. Functional deficiency in the protein disulfide isomerase anterior gradient 2 (AGR2) has been linked with CD and leads to epithelial cell ER stress and ileocolitis in mice and humans. Here, we show that ileal expression of AGR2 correlates with mucosal Enterobactericeae abundance in human inflammatory bowel disease (IBD) and that Agr2 deletion leads to ER-stress-dependent expansion of mucosal-associated adherent-invasive Escherichia coli (AIEC), which drives Th17 cell ileocolitis in mice. Mechanistically, our data reveal that AIEC-induced epithelial cell ER stress triggers CD103 + dendritic cell production of interleukin-23 (IL-23) and that IL-23R is required for ileocolitis in Agr2 -/- mice. Overall, these data reveal a specific and reciprocal interaction of the expansion of the CD pathobiont AIEC with ER-stress-associated ileocolitis and highlight a distinct cellular mechanism for IL-23-dependent ileocolitis.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P01 DK094779 United States DK NIDDK NIH HHS; P40 OD010995 United States OD NIH HHS; P30 DK034987 United States DK NIDDK NIH HHS; R01 DK122042 United States DK NIDDK NIH HHS; R01 DK120985 United States DK NIDDK NIH HHS; R01 DK053347 United States DK NIDDK NIH HHS; R01 DK090967 United States DK NIDDK NIH HHS; R01 DK114252 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: AIEC; Agr2; CP: Immunology; CP: Microbiology; ER stress; IL-23; Th17; ileitis
المشرفين على المادة: 0 (Interleukin-23)
0 (Mucoproteins)
0 (Oncogene Proteins)
0 (Agr2 protein, mouse)
تواريخ الأحداث: Date Created: 20221117 Date Completed: 20221122 Latest Revision: 20230720
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9805753
DOI: 10.1016/j.celrep.2022.111637
PMID: 36384110
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2022.111637