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The nuclear factor-kappa light chain enhancer of activated B cells (NF-\u03baB) signaling pathway is particularly relevant in the intestine, as it seems to play a dual role. Whereas NF-\u03baB protects intestinal epithelium against various noxious stimuli, the same pathway mediates intestinal inflammatory diseases by inducing pro-inflammatory gene expression. The availability of appropriate in vitro models of the intestinal epithelium is crucial for further understanding the contribution of NF-\u03baB in physiological and pathological processes and advancing in the development of drugs and therapies against gut diseases. Here we established, characterized, and validated three-dimensional cultures of intestinal organoids obtained from biopsies of NF-\u03baB-RE-Luc mice. The NF-\u03baB-RE-Luc intestinal organoids derived from different intestine regions recreated the cellular composition of the tissue and showed a reporter responsiveness similar to the in vivo murine model. When stimulated with TNF-\u03b1, jejunum-derived NF-\u03baB-RE-Luc-reporter organoids, provided a useful model to evaluate the anti-inflammatory effects of natural and synthetic compounds. These reporter organoids are valuable tools to explore the epithelial TNF-\u03b1-induced NF-\u03baB contribution in the small intestine, being a reliable alternative method while helping to reduce the use of laboratory animals for experimentation.<\/jats:p>","DOI":"10.1038\/s41598-022-18556-3","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T06:08:05Z","timestamp":1661321285000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Jejunum-derived NF-\u03baB reporter organoids as 3D models for the study of TNF-alpha-induced inflammation"],"prefix":"10.1038","volume":"12","author":[{"given":"Hellen","family":"Daghero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Doffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Yozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Verdes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Crispo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Bollati-Fogol\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Pagotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"18556_CR1","first-page":"14","volume":"4","author":"N Shi","year":"2017","unstructured":"Shi, N., Li, N., Duan, X. & Niu, H. 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The Supplementary Information file now accompanies the original Article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14425"}}