RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3

Christopher P Dillon; Ricardo Weinlich; Diego A Rodriguez; James G Cripps; Giovanni Quarato; Prajwal Gurung; Katherine C Verbist; Taylor L Brewer; Fabien Llambi; Yi-Nan Gong; Laura J Janke; Michelle A Kelliher; Thirumala-Devi Kanneganti; Douglas R Green

doi:10.1016/j.cell.2014.04.018

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RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3

Journal article

Open access

Peer reviewed

RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3

Christopher P Dillon, Ricardo Weinlich, Diego A Rodriguez, James G Cripps, Giovanni Quarato, Prajwal Gurung, Katherine C Verbist, Taylor L Brewer, Fabien Llambi, Yi-Nan Gong, …

Cell, Vol.157(5), pp.1189-1202

05/22/2014

DOI: 10.1016/j.cell.2014.04.018

PMCID: PMC4068710

PMID: 24813850

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Abstract

Receptor-interacting protein kinase (RIPK)-1 is involved in RIPK3-dependent and -independent signaling pathways leading to cell death and/or inflammation. Genetic ablation of ripk1 causes postnatal lethality, which was not prevented by deletion of ripk3, caspase-8, or fadd. However, animals that lack RIPK1, RIPK3, and either caspase-8 or FADD survived weaning and matured normally. RIPK1 functions in vitro to limit caspase-8-dependent, TNFR-induced apoptosis, and animals lacking RIPK1, RIPK3, and TNFR1 survive to adulthood. The role of RIPK3 in promoting lethality in ripk1(-/-) mice suggests that RIPK3 activation is inhibited by RIPK1 postbirth. Whereas TNFR-induced RIPK3-dependent necroptosis requires RIPK1, cells lacking RIPK1 were sensitized to necroptosis triggered by poly I:C or interferons. Disruption of TLR (TRIF) or type I interferon (IFNAR) signaling delayed lethality in ripk1(-/-)tnfr1(-/-) mice. These results clarify the complex roles for RIPK1 in postnatal life and provide insights into the regulation of FADD-caspase-8 and RIPK3-MLKL signaling by RIPK1.

Animals, Newborn

Receptor-Interacting Protein Serine-Threonine Kinases - metabolism

Mice, Inbred C57BL

Caspase 8 - metabolism

Fas-Associated Death Domain Protein - metabolism

Tumor Necrosis Factors - metabolism

Receptors, Tumor Necrosis Factor, Type I - metabolism

Receptors, Tumor Necrosis Factor, Type I - genetics

Adaptor Proteins, Vesicular Transport - metabolism

Embryo, Mammalian - metabolism

Caspase 8 - genetics

Genes, Lethal

Inflammation - metabolism

Receptor-Interacting Protein Serine-Threonine Kinases - genetics

Animals

Embryo, Mammalian - cytology

Cell Death

Interferons - metabolism

Mice

Apoptosis

Fibroblasts - metabolism

Details

Title: Subtitle: RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3
Creators: Christopher P Dillon - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Ricardo Weinlich - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Diego A Rodriguez - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
James G Cripps - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Giovanni Quarato - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Katherine C Verbist - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Taylor L Brewer - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Fabien Llambi - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Yi-Nan Gong - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Laura J Janke - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Michelle A Kelliher - Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Douglas R Green - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: douglas.green@stjude.org
Resource Type: Journal article
Publication Details: Cell, Vol.157(5), pp.1189-1202
DOI: 10.1016/j.cell.2014.04.018
PMID: 24813850
PMCID: PMC4068710
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: R01 AI075118 / NIAID NIH HHS P30 CA021765 / NCI NIH HHS R01 AI044828 / NIAID NIH HHS AI44828 / NIAID NIH HHS R01 CA169291 / NCI NIH HHS CA169291 / NCI NIH HHS
Language: English
Date published: 05/22/2014
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094359602771

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