دورية أكاديمية
أعرض في EDS

Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune Gastritis.

التفاصيل البيبلوغرافية
العنوان: Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune Gastritis.
المؤلفون: Bockerstett KA; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Petersen CP; Nashville Veterans Affairs Medical Center, Department of Surgery, Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Noto CN; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Kuehm LM; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Wong CF; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Ford EL; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Teague RM; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri., Mills JC; Division of Gastroenterology, Department of Medicine, Pathology and Immunology, Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri., Goldenring JR; Nashville Veterans Affairs Medical Center, Department of Surgery, Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee., DiPaolo RJ; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri. Electronic address: richard.dipaolo@health.slu.edu.
المصدر: Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2020; Vol. 10 (3), pp. 561-579. Date of Electronic Publication: 2020 May 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Gastroenterological Association Country of Publication: United States NLM ID: 101648302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-345X (Electronic) Linking ISSN: 2352345X NLM ISO Abbreviation: Cell Mol Gastroenterol Hepatol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Philadelphia, PA : American Gastroenterological Association, [2015]-
مواضيع طبية MeSH: Autoimmune Diseases/*drug therapy , Gastric Mucosa/*pathology , Gastritis/*drug therapy , Interleukins/*administration & dosage , Precancerous Conditions/*prevention & control, Animals ; Atrophy/immunology ; Atrophy/pathology ; Atrophy/prevention & control ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Chronic Disease/drug therapy ; Disease Models, Animal ; Female ; Gastric Mucosa/cytology ; Gastric Mucosa/drug effects ; Gastric Mucosa/immunology ; Gastritis/diagnosis ; Gastritis/immunology ; Gastritis/pathology ; Humans ; Male ; Metaplasia/immunology ; Metaplasia/pathology ; Metaplasia/prevention & control ; Mice ; Mice, Knockout ; Minor Histocompatibility Antigens/genetics ; Precancerous Conditions/immunology ; Precancerous Conditions/pathology ; Receptors, Cytokine/genetics ; Recombinant Proteins/administration & dosage ; Severity of Illness Index
مستخلص: Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis.
Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3 -/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues.
Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes.
Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell-mediated inflammation in the gastric mucosa.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 DK094989 United States DK NIDDK NIH HHS; R01 DK101332 United States DK NIDDK NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; F31 DK104600 United States DK NIDDK NIH HHS; I01 BX000930 United States BX BLRD VA; P30 CA091842 United States CA NCI NIH HHS; F30 DK118873 United States DK NIDDK NIH HHS; R01 DK110406 United States DK NIDDK NIH HHS; P30 DK052574 United States DK NIDDK NIH HHS; R01 DK105129 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: Immune Regulation; Lymphocyte; Mouse Model; Transcription
المشرفين على المادة: 0 (Ebi3 protein, mouse)
0 (Il27 protein, mouse)
0 (Interleukins)
0 (Minor Histocompatibility Antigens)
0 (Receptors, Cytokine)
0 (Recombinant Proteins)
تواريخ الأحداث: Date Created: 20200508 Date Completed: 20210907 Latest Revision: 20240922
رمز التحديث: 20240922
مُعرف محوري في PubMed: PMC7399182
DOI: 10.1016/j.jcmgh.2020.04.014
PMID: 32376420
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-345X
DOI:10.1016/j.jcmgh.2020.04.014