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IL-10 signaling prevents gluten-dependent intraepithelial CD4 + cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine.

التفاصيل البيبلوغرافية
العنوان: IL-10 signaling prevents gluten-dependent intraepithelial CD4 + cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine.
المؤلفون: Costes LMM; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., Lindenbergh-Kortleve DJ; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., van Berkel LA; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., Veenbergen S; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., Raatgeep HRC; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., Simons-Oosterhuis Y; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., van Haaften DH; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands., Karrich JJ; Department of Hematology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands., Escher JC; Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands., Groeneweg M; Department of Pediatrics, Maasstad Hospital, Rotterdam, 3079 DZ, The Netherlands., Clausen BE; Institute for Molecular Medicine, University Medical Center of Johannes Gutenberg University, Mainz, 55131, Germany., Cupedo T; Department of Hematology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands., Samsom JN; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands. j.samsom@erasmusmc.nl.
المصدر: Mucosal immunology [Mucosal Immunol] 2019 Mar; Vol. 12 (2), pp. 479-490. Date of Electronic Publication: 2018 Dec 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
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: CD4-Positive T-Lymphocytes/*immunology , Celiac Disease/*immunology , Interleukin-10/*metabolism , Intestinal Mucosa/*immunology , Intraepithelial Lymphocytes/*immunology, Animals ; Cell Death ; Cell Differentiation ; Cell Movement ; Child ; Cytotoxicity, Immunologic ; Glutens/immunology ; Granzymes/metabolism ; Homeostasis ; Humans ; Immune Tolerance ; Interleukin-10/genetics ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Signal Transduction ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism
مستخلص: Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive. We have demonstrated that under homeostatic conditions in mice, gluten drives the differentiation of anti-inflammatory T cells producing large amounts of the immunosuppressive cytokine interleukin-10 (IL-10). Here we addressed whether this dominant IL-10 axis prevents gluten-dependent infiltration of activated cytotoxic IEL and subsequent small intestinal enteropathy. We demonstrate that IL-10 regulation prevents gluten-induced cytotoxic inflammatory IEL infiltration. In particular, IL-10 suppresses gluten-induced accumulation of a specialized population of cytotoxic CD4 + CD8αα + IEL (CD4 + CTL) expressing Tbx21, Ifng, and Il21, and a disparate non-cytolytic CD4 + CD8α - IEL population expressing Il17a, Il21, and Il10. Concomitantly, IL-10 suppresses gluten-dependent small intestinal epithelial hyperproliferation and upregulation of stress-induced molecules on epithelial cells. Remarkably, frequencies of granzyme B + CD4 + CD8α + IEL are increased in pediatric celiac disease patient biopsies. These findings demonstrate that IL-10 is pivotal to prevent gluten-induced small intestinal inflammation and epithelial damage, and imply that CD4 + CTL are potential new players into these processes.
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المشرفين على المادة: 0 (T-Box Domain Proteins)
0 (T-box transcription factor TBX21)
130068-27-8 (Interleukin-10)
8002-80-0 (Glutens)
EC 3.4.21.- (Granzymes)
تواريخ الأحداث: Date Created: 20181214 Date Completed: 20190624 Latest Revision: 20230203
رمز التحديث: 20240628
DOI: 10.1038/s41385-018-0118-0
PMID: 30542112
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-3456
DOI:10.1038/s41385-018-0118-0