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Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals

التفاصيل البيبلوغرافية
العنوان: Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals
المؤلفون: Papoutsopoulou S., Pollock L., Walker C., Tench W., Samad S.S., Bergey F., Lenzi L., Sheibani-Tezerji R., Rosenstiel P., Alam M.T., Martins Dos Santos V.A.P., Müller W., Campbell B.J.
المصدر: Frontiers in Immunology ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109015803&doi=10.3389%2ffimmu.2021.690817&partnerID=40&md5=f8a980780957b689b772d006a0cb3fd8Test
سنة النشر: 2021
المجموعة: University of Thessaly Institutional Repository / Ιδρυματικό Αποθετήριο Πανεπιστημίου Θεσσαλίας
مصطلحات موضوعية: antiinflammatory agent, bovine serum albumin, edetic acid, flagellin, gamma interferon inducible protein 10, immunoglobulin enhancer binding protein, interleukin 10, lipopolysaccharide, luciferase, luciferin, macrophage inflammatory protein 3alpha, transposase, tumor necrosis factor, animal experiment, animal model, animal tissue, Article, C57BL 6 mouse, Ccl20 gene, centrifugation, chromatin, controlled study, Cxcl10 gene, down regulation, enteroid, enzyme linked immunosorbent assay, gene, gene expression, gene expression assay, gene overexpression
الوصف: Interleukin 10 (IL-10) is a pleiotropic, anti-inflammatory cytokine that has a major protective role in the intestine. Although its production by cells of the innate and adaptive immune system has been extensively studied, its intrinsic role in intestinal epithelial cells is poorly understood. In this study, we utilised both ATAC sequencing and RNA sequencing to define the transcriptional response of murine enteroids to tumour necrosis factor (TNF). We identified that the key early phase drivers of the transcriptional response to TNF within intestinal epithelium were NFκB transcription factor dependent. Using wild-type and Il10−/− enteroid cultures, we showed an intrinsic, intestinal epithelium specific effect of IL-10 deficiency on TNF-induced gene transcription, with significant downregulation of identified NFκB target genes Tnf, Ccl20, and Cxcl10, and delayed overexpression of NFκB inhibitor encoding genes, Nfkbia and Tnfaip3. IL-10 deficiency, or immunoblockade of IL-10 receptor, impacted on TNF-induced endogenous NFκB activity and downstream NFκB target gene transcription. Intestinal epithelium-derived IL-10 appears to play a crucial role as a positive regulator of the canonical NFκB pathway, contributing to maintenance of intestinal homeostasis. This is particularly important in the context of an inflammatory environment and highlights the potential for future tissue-targeted IL-10 therapeutic intervention. © Copyright © 2021 Papoutsopoulou, Pollock, Walker, Tench, Samad, Bergey, Lenzi, Sheibani-Tezerji, Rosenstiel, Alam, Martins Dos Santos, Müller and Campbell.
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 16643224
العلاقة: http://hdl.handle.net/11615/77904Test
DOI: 10.3389/fimmu.2021.690817
الإتاحة: https://doi.org/10.3389/fimmu.2021.690817Test
http://hdl.handle.net/11615/77904Test
رقم الانضمام: edsbas.A6536568
قاعدة البيانات: BASE
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