RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition
-
- William J. Kaiser
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Lisa P. Daley-Bauer
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Roshan J. Thapa
- Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111; and
-
- Pratyusha Mandal
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Scott B. Berger
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426
-
- Chunzi Huang
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Aarthi Sundararajan
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Hongyan Guo
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Linda Roback
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- Samuel H. Speck
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
-
- John Bertin
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426
-
- Peter J. Gough
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426
-
- Siddharth Balachandran
- Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111; and
-
- Edward S. Mocarski
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
抄録
<jats:title>Significance</jats:title> <jats:p>The protein kinase receptor interacting protein 1 controls signaling via death receptors, Toll-like receptors, and retinoic acid-inducible gene 1-like receptors, dictating inflammatory outcomes as broad as cytokine activation and cell death. RIP1 makes a vital contribution during development, evident from the fact that RIP1-deficient mice die soon after birth. Here, we show that a kinase-independent function of RIP1 dampens the consequences of innate immune cell death. During parturition, RIP1 prevents the lethal consequences of RIP3-dependent necroptosis as well as caspase 8 (Casp8)-dependent apoptosis. In contrast to the RIP1-deficient phenotype, mice lacking a combination of RIP1, RIP3, and Casp8 are born and mature into viable, fertile, and immunocompetent adults. These results demonstrate the important protective role of RIP1 against physiologic and microbial death cues encountered at birth.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 111 (21), 7753-7758, 2014-05-12
Proceedings of the National Academy of Sciences