Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease

doi:10.1038/s41586-019-1828-5

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1828-5
	Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease
	Lalaoui, Najoua 1,2; Boyden, Steven E.3; Oda, Hirotsugu 3; Wood, Geryl M.3; Stone, Deborah L.3; Chau, Diep 1; Liu, Lin 1,2; Stoffels, Monique 3; Kratina, Tobias 1; Lawlor, Kate E.4,5; Zaal, Kristien J. M.6; Hoffmann, Patrycja M.3; Etemadi, Nima 1,2; Shield-Artin, Kristy 1,2; Biben, Christine 1,2; Tsai, Wanxia Li 7; Blake, Mary D.7; Kuehn, Hye Sun 8; Yang, Dan 9; Anderton, Holly 1,2; Silke, Natasha 1; Wachsmuth, Laurens 10,11,12; Zheng, Lixin 13,14; Moura, Natalia Sampaio 3; Beck, David B.3; Gutierrez-Cruz, Gustavo 15; Ombrello, Amanda K.3; Pinto-Patarroyo, Gineth P.3; Kueh, Andrew J.1,2; Herold, Marco J.1,2; Hall, Cathrine 1; Wang, Hongying 3; Chae, Jae Jin 3; Dmitrieva, Natalia I.9; McKenzie, Mark 1,2; Light, Amanda 1; Barham, Beverly K.3; Jones, Anne 3; Romeo, Tina M.3; Zhou, Qing 3; Aksentijevich, Ivona 3; Mullikin, James C.16; Gross, Andrew J.17; Shum, Anthony K.18; Hawkins, Edwin D.1,2; Masters, Seth L.1,2; Lenardo, Michael J.13,14; Boehm, Manfred 9; Rosenzweig, Sergio D.8; Pasparakis, Manolis 10,11,12; Voss, Anne K.1,2; Gadina, Massimo 7; Kastner, Daniel L.3; Silke, John 1,2
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7788 页码:103-+
文章类型	Article
语种	英语
国家	Australia; USA; Germany
英文关键词	RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term ' cleavage-resistant RIPK1-induced autoinflammatory syndrome' . To define the mechanism for this disease, we generated a cleavage-resistant Ripk1(D325A) mutant mouse strain. Whereas Ripk1(-/-) mice died postnatally from systemic inflammation, Ripk1(D325A/D325A) mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1(D325A/D325A) embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1(D325A/D325A) and Ripk1(D325A/+) cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1(D325A/+) mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000505617400034
WOS关键词	DOMAIN KINASE RIP ; CELL-DEATH ; PSEUDOKINASE MLKL ; NECROPTOSIS ; ACTIVATION ; PHOSPHORYLATION ; INFLAMMATION ; EXPRESSION ; RECEPTORS ; LETHALITY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281085
专题	地球科学资源环境科学气候变化
作者单位	1.Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia; 2.Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia; 3.NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA; 4.Hudson Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic, Australia; 5.Monash Univ, Dept Mol & Translat Sci, Clayton, Vic, Australia; 6.NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA; 7.NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA; 8.NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA; 9.NHLBI, Translat Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA; 10.Univ Cologne, Inst Genet, Cologne, Germany; 11.Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany; 12.Univ Cologne, Ctr Mol Med CMMC, Cologne, Germany; 13.NIAID, Mol Dev Immune Syst Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA; 14.NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA; 15.NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA; 16.NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA; 17.Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA; 18.Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94143 USA
推荐引用方式 GB/T 7714	Lalaoui, Najoua,Boyden, Steven E.,Oda, Hirotsugu,et al. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease[J]. NATURE,2020,577(7788):103-+.
APA	Lalaoui, Najoua.,Boyden, Steven E..,Oda, Hirotsugu.,Wood, Geryl M..,Stone, Deborah L..,...&Silke, John.(2020).Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease.NATURE,577(7788),103-+.
MLA	Lalaoui, Najoua,et al."Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease".NATURE 577.7788(2020):103-+.