期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7442
关键词
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资金
- NHMRC [1046986, 461221, 1016701, 1037321, 1043414, 1024839, 1051210, 606788, 1035502]
- ARC [FT130100166, DE12010340, FT 100100100]
- WEHI de Burgh Fellowship
- Rebecca Cooper Foundation
- Juvenile Diabetes Research Foundation
- Leukaemia and Lymphoma Society
- Australian Cancer Research Foundation
- Catalyst Therapeutics
- Novo Nordisk Foundation
- Lundbeck Foundation
- Swiss National Science Foundation (SNSF) [PA00P3_126249]
- Danish Council for Independent Research-Natural Sciences
- joint Cure Cancer/Leukemia Foundation
- CIHR
- Australian Research Council [FT130100166] Funding Source: Australian Research Council
- Swiss National Science Foundation (SNF) [PA00P3_126249] Funding Source: Swiss National Science Foundation (SNF)
Intracellular 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-kappa B and MAP kinases. Receptor interacting protein kinase 2 (RIPK2) is critical for NOD-mediated NF-kappa B activation and cytokine production. Here we develop and characterize a selective RIPK2 kinase inhibitor, WEHI-345, which delays RIPK2 ubiquitylation and NF-kappa B activation downstream of NOD engagement. Despite only delaying NF-kappa B 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.
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