The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions
Open accessAbstract
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.
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“Inhibitor of nuclear factor kappa B kinase subunit gamma (IKBKG; best known as NEMO) also prevents RIPK1-driven intestinal inflammation and epithelial cell death, although the underlying molecular mechanisms remain poorly understood [511]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [511]
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Metadata
- Authors
- Vlantis, K., Wullaert, A., Polykratis, A., Kondylis, V., Dannappel, M., Schwarzer, R., Welz, P., Corona, T., Walczak, H., Weih, F., Klein, U., Kelliher, M., & Pasparakis, M.
- Affiliations
- University of Cologne (DE)
- University College London (GB)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Herbert Irving Comprehensive Cancer Center (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Pasparakis, Manolis
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 44
- Issue
- 3
- Pages
- 553-567
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4803910
- OpenAlex
- W2299243013
- Cited by
- 189
- References
- 38
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 22 · 2023: 19 · 2022: 16 · 2021: 20 · 2020: 24 · 2019: 20 · 2018: 25 · 2017: 19 · 2016: 4
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Funders
- European Commission (223151, 223404)
- Deutsche Forschungsgemeinschaft (SPP-1656, SFB 670)
- Universität Ulm
- National Institutes of Health
- Genentech
- National Institute of Allergy and Infectious Diseases (R01AI075118)
- FP7 Ideas: European Research Council (323040)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- NEMO, RIPK1, NF-κB, intestinal epithelial cells, epithelial cell death, chronic intestinal inflammation, colitis, inflammatory bowel disease, FADD, RIPK3, microbiota, RelA, c-Rel, RelB, RIPK1 inhibitors
- MeSH terms
- Animals, Cells, Cultured, Humans, Intestinal Mucosa, Mice, Inbred C57BL, Inflammatory Bowel Diseases, NF-kappa B, Apoptosis, Mice, Knockout, Paneth Cells, Proto-Oncogene Proteins c-rel, Intracellular Signaling Peptides and Proteins, Mice, Transcription Factor RelB, Transcription Factor RelA, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases
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