دورية أكاديمية
أعرض في EDS

IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4 + T cells: relevance to inflammatory bowel disease.

التفاصيل البيبلوغرافية
العنوان: IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4 + T cells: relevance to inflammatory bowel disease.
المؤلفون: Veenbergen S; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands. s.veenbergen@erasmusmc.nl.; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. s.veenbergen@erasmusmc.nl., Li P; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Raatgeep HC; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., Lindenbergh-Kortleve DJ; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., Simons-Oosterhuis Y; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., Farrel A; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Costes LMM; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., Joosse ME; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., van Berkel LA; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., de Ruiter LF; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., van Leeuwen MA; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands., Winter D; Department of Pediatric Gastroenterology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands., Holland SM; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Freeman AF; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Wakabayashi Y; DNA Sequencing and Genomics Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Zhu J; DNA Sequencing and Genomics Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA., de Ridder L; Department of Pediatric Gastroenterology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands., Driessen GJ; Department of Pediatric Infectious Disease and Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.; Haga Teaching Hospital, Juliana Children's Hospital, The Hague, The Netherlands., Escher JC; Department of Pediatric Gastroenterology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands., Leonard WJ; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Samsom JN; Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands. j.samsom@erasmusmc.nl.
المصدر: Mucosal immunology [Mucosal Immunol] 2019 Sep; Vol. 12 (5), pp. 1201-1211. Date of Electronic Publication: 2019 Aug 15.
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: Signal Transduction*, CD4-Positive T-Lymphocytes/*immunology , CD4-Positive T-Lymphocytes/*metabolism , Dendritic Cells/*immunology , Dendritic Cells/*metabolism , Interferon-gamma/*metabolism , Interleukin-10/*metabolism , Interleukin-1beta/*metabolism, Adolescent ; Cell Communication ; Child ; Disease Susceptibility ; Humans ; Inflammatory Bowel Diseases/etiology ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Inflammatory Bowel Diseases/therapy
مستخلص: Uncontrolled interferon γ (IFNγ)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. A better understanding of how IL-10 exerts its suppressive function may allow identification of individuals with suboptimal IL-10 function among the heterogeneous population of IBD patients. Using cells from patients with an IL10RA deficiency or STAT3 mutations, we demonstrate that IL-10 signaling in monocyte-derived dendritic cells (moDCs), but not T cells, is essential for controlling IFNγ-secreting CD4 + T cells. Deficiency in IL-10 signaling dramatically increased IL-1β release by moDCs. IL-1β boosted IFNγ secretion by CD4 + T cells either directly or indirectly by stimulating moDCs to secrete IL-12. As predicted a signature of IL-10 dysfunction was observed in a subgroup of pediatric IBD patients having higher IL-1β expression in activated immune cells and macroscopically affected intestinal tissue. In agreement, reduced IL10RA expression was detected in peripheral blood mononuclear cells and a subgroup of pediatric IBD patients exhibited diminished IL-10 responsiveness. Our data unveil an important mechanism by which IL-10 controls IFNγ-secreting CD4 + T cells in humans and identifies IL-1β as a potential classifier for a subgroup of IBD patients.
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معلومات مُعتمدة: Z99 HL999999 United States ImNIH Intramural NIH HHS
المشرفين على المادة: 0 (IL10 protein, human)
0 (IL1B protein, human)
0 (Interleukin-1beta)
130068-27-8 (Interleukin-10)
82115-62-6 (Interferon-gamma)
تواريخ الأحداث: Date Created: 20190817 Date Completed: 20200420 Latest Revision: 20230203
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6752724
DOI: 10.1038/s41385-019-0194-9
PMID: 31417161
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-3456
DOI:10.1038/s41385-019-0194-9