Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 116 (2018-12-29), Heft 3
Online
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Zugriff:
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.
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Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases
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| Autor/in / Beteiligte Person: | Rohlfs, Meino ; Shteyer, Eyal ; Eman Al Idrissi ; Schwarz, Klaus ; Pannicke, Ulrich ; Führer, Marita ; Koletzko, Sibylle ; Walz, Christoph ; Sepulveda, Fernando E. ; Snapper, Scott B. ; Klein, Christoph ; Bouzidi, Amira ; Field, Michael ; Turner, Dan ; Muise, Aleixo M. ; Hamza Ali Alghamdi ; Li, Yue ; Kotlarz, Daniel ; Hornung, Veit ; Socha, Piotr ; Gil, Marine ; Lehle, Anna S. ; Gaidt, Moritz M. ; Geneviève de Saint Basile ; Baumann, Bernd ; Conca, Raffaele ; Magg, Thomas ; Boukari, Rachida ; Liu, Yanshan ; Warner, Neil ; Hollizeck, Sebastian ; Mordechai, Slae ; Klaudel-Dreszler, Maja ; Bahrami, Ehsan ; Belbouab, Reda ; Hönig, Manfred ; Dr von Hauner Children's Hospital [Munich, Germany] ; Ludwig-Maximilians-Universität München (LMU) ; Boston Children's Hospital ; The Hospital for sick children [Toronto] (SickKids) ; Faculté de médecine d'Alger ; Université d'Alger 1 (Benyoucef Benkhedda) ; Gene Center LMU Munich, Feodor-Lynen Strasse 25, 81377 Munich ; King Fahad Med City, Dept Pediat ; Imagine - Institut des maladies génétiques (IMAGINE - U1163) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Developpement Normal et Pathologique du Système Immunitaire ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Clinical Medical Center ; Ludwig Maximilians University-Dr. von Haunersches Kinderspital ; Institut für klinische Transfusionsmedizin und Immungenetik und Institut für Transfusionsmedizin ; Universitätsklinikum Ulm - University Hospital of Ulm ; Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
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| Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 116 (2018-12-29), Heft 3 |
| Veröffentlichung: | 2018 |
| Medientyp: | unknown |
| ISSN: | 1091-6490 (print) ; 0027-8424 (print) |
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