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dc.contributor.authorNachbur, Uelien
dc.contributor.authorStafford, Che Aen
dc.contributor.authorBankovacki, Aleksandraen
dc.contributor.authorZhan, Yifanen
dc.contributor.authorLindqvist, Lisa Men
dc.contributor.authorFiil, Berthe Ken
dc.contributor.authorKhakham, Yelenaen
dc.contributor.authorKo, Hyun-Jaen
dc.contributor.authorSandow, Jarrod Jen
dc.contributor.authorFalk, Hendriken
dc.contributor.authorHolien, Jessica Ken
dc.contributor.authorChau, Diepen
dc.contributor.authorHildebrand, Joanneen
dc.contributor.authorVince, James Een
dc.contributor.authorSharp, Phillip Pen
dc.contributor.authorWebb, Andrew Ien
dc.contributor.authorJackman, Katherine Aen
dc.contributor.authorMühlen, Sabrinaen
dc.contributor.authorKennedy, Catherine Len
dc.contributor.authorLowes, Kym Nen
dc.contributor.authorMurphy, James Men
dc.contributor.authorGyrd-Hansen, Madsen
dc.contributor.authorParker, Michael Wen
dc.contributor.authorHartland, Elizabeth Len
dc.contributor.authorLew, Andrew Men
dc.contributor.authorHuang, David C Sen
dc.contributor.authorLessene, Guillaumeen
dc.contributor.authorSilke, Johnen
dc.identifier.citationNature Communications 2015; 6(): 6442en
dc.description.abstractIntracellular nucleotide binding and oligomerization domain (NOD) receptors recognize antigens including bacterial peptidoglycans and initiate immune responses by triggering the production of pro-inflammatory cytokines through activating NF-κB and MAP kinases. Receptor interacting protein kinase 2 (RIPK2) is critical for NOD-mediated NF-κB activation and cytokine production. Here we develop and characterize a selective RIPK2 kinase inhibitor, WEHI-345, which delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. Despite only delaying NF-κB activation on NOD stimulation, WEHI-345 prevents cytokine production in vitro and in vivo and ameliorates experimental autoimmune encephalomyelitis in mice. Our study highlights the importance of the kinase activity of RIPK2 for proper immune responses and demonstrates the therapeutic potential of inhibiting RIPK2 in NOD-driven inflammatory diseases.en
dc.titleA RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production.en
dc.typeJournal Articleen
dc.identifier.journaltitleNature Communicationsen
dc.identifier.affiliationDepartment of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Campus, 245 Burgundy Street, Heidelberg, Victoria 3084, Australiaen
dc.identifier.affiliationACRF Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australiaen
dc.identifier.affiliationDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australiaen
dc.identifier.affiliationLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UKen
dc.identifier.affiliationDepartment of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australiaen
dc.identifier.affiliationCancer Therapeutics CRC, Bundoora, Victoria 3083, Australiaen
dc.identifier.affiliationDepartment of Disease Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmarken
dc.identifier.affiliationACRF Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australiaen
dc.type.austinJournal Articleen
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
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