| Literature DB >> 30591564 |
Yue Li1, Marita Führer2, Ehsan Bahrami1, Piotr Socha3, Maja Klaudel-Dreszler3, Amira Bouzidi1, Yanshan Liu1, Anna S Lehle1, Thomas Magg1, Sebastian Hollizeck1, Meino Rohlfs1, Raffaele Conca1, Michael Field4, Neil Warner5,6, Slae Mordechai7, Eyal Shteyer8, Dan Turner8,9, Rachida Boukari10, Reda Belbouab10, Christoph Walz11, Moritz M Gaidt12,13, Veit Hornung12,13, Bernd Baumann14, Ulrich Pannicke2, Eman Al Idrissi15, Hamza Ali Alghamdi15, Fernando E Sepulveda16,17, Marine Gil16,17, Geneviève de Saint Basile16,17,18, Manfred Hönig19, Sibylle Koletzko1,9, Aleixo M Muise5,6,9,20,21, Scott B Snapper4,9,22,23, Klaus Schwarz2,24, Christoph Klein1,9, Daniel Kotlarz25,9.
Abstract
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical regulator of cell death and inflammation, but its relevance for human disease pathogenesis remains elusive. Studies of monogenic disorders might provide critical insights into disease mechanisms and therapeutic targeting of RIPK1 for common diseases. Here, we report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in RIPK1 presenting with primary immunodeficiency and/or intestinal inflammation. Mutations in RIPK1 were associated with reduced NF-κB activity, defective differentiation of T and B cells, increased inflammasome activity, and impaired response to TNFR1-mediated cell death in intestinal epithelial cells. The characterization of RIPK1-deficient patients highlights the essential role of RIPK1 in controlling human immune and intestinal homeostasis, and might have critical implications for therapies targeting RIPK1.Entities:
Keywords: inflammatory bowel diseases; primary immunodeficiency; rare diseases
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Year: 2018 PMID： 30591564 PMCID： PMC6338855 DOI： 10.1073/pnas.1813582116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205