{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:30:20Z","timestamp":1793035820982,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102172\/B\/13\/Z"],"award-info":[{"award-number":["102172\/B\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["MR\/P023606\/1"],"award-info":[{"award-number":["MR\/P023606\/1"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council, UK","doi-asserted-by":"publisher","award":["102172\/B\/13\/Z"],"award-info":[{"award-number":["102172\/B\/13\/Z"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council, UK","doi-asserted-by":"publisher","award":["MR\/P023606\/1"],"award-info":[{"award-number":["MR\/P023606\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a major protective role against intestinal inflammation. We recently revealed that intestinal epithelial cells in vitro regulate NF\u03baB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here in this study, we investigated the impact of IL-10 deficiency on the NF\u03baB pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, I\u03baB\u03b1, and A20 gene and protein expression in the small intestine of steady-state or TNF-injected Il10\u2212\/\u2212 mice, compared to wild-type C57BL6\/J counterparts. Upon TNF injection, tissue from the small intestine showed upregulation of NF\u03baB p65[RelA] activity, which was totally diminished in Il10\u2212\/\u2212 mice and correlated with reduced levels of TNF, I\u03baB\u03b1, and A20 expression. In serum, whilst IgA levels were noted to be markedly downregulated in IL-10-deficient- mice, normal levels of mucosal IgA were seen in intestine mucosa. Importantly, dysregulated cytokine\/chemokine levels were observed in both serum and intestinal tissue lysates from na\u00efve, as well as TNF-injected Il10\u2212\/\u2212 mice. These data further support the importance of the IL-10-canonical NF\u03baB signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo.<\/jats:p>","DOI":"10.3390\/biology11101377","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T21:12:53Z","timestamp":1663708373000},"page":"1377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interleukin-10 Deficiency Impacts on TNF-Induced NF\u03baB Regulated Responses In Vivo"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-8508","authenticated-orcid":false,"given":"Stamatia","family":"Papoutsopoulou","sequence":"first","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Pollock","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"Department of Molecular Physiology & Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-0323","authenticated-orcid":false,"given":"Jonathan M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Pathobiology and Population Sciences, Royal Veterinary College, Hatfield AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1294-4693","authenticated-orcid":false,"given":"Maya M. L. F.","family":"Abdul-Mahdi","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"School of Life Sciences, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyhaneh","family":"Dobbash","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"School of Life Sciences, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie A.","family":"Duckworth","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"Department of Molecular Physiology & Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7407-012X","authenticated-orcid":false,"given":"Barry J.","family":"Campbell","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK"},{"name":"Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3389\/fimmu.2020.01315","article-title":"IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology","volume":"11","author":"Wei","year":"2020","journal-title":"Front. 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