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Publication

RIPK3 Activation Leads to Cytokine Synthesis that Continues after Loss of Cell Membrane Integrity.

Cell reports | 2019

Necroptosis is a form of programmed cell death that is defined by activation of the kinase RIPK3 and subsequent cell membrane permeabilization by the effector MLKL. RIPK3 activation can also promote immune responses via production of cytokines and chemokines. How active cytokine production is coordinated with the terminal process of necroptosis is unclear. Here, we report that cytokine production continues within necroptotic cells even after they have lost cell membrane integrity and irreversibly committed to death. This continued cytokine production is dependent on mRNA translation and requires maintenance of endoplasmic reticulum integrity that remains after plasma membrane integrity is lost. The continued translation of cytokines by cellular corpses contributes to necroptotic cell uptake by innate immune cells and priming of adaptive immune responses to antigens associated with necroptotic corpses. These findings imply that cell death and production of inflammatory mediators are coordinated to optimize the immunogenicity of necroptotic cells.

Pubmed ID: 31461645 RIS Download

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Associated grants

Agency: NIAID NIH HHS, United States
Id: R01 AI132595
Agency: NIGMS NIH HHS, United States
Id: T32 GM007270
Agency: NCI NIH HHS, United States
Id: R01 CA228098
Agency: NIAID NIH HHS, United States
Id: R37 AI044828
Agency: NCI NIH HHS, United States
Id: P30 CA021765
Agency: NCI NIH HHS, United States
Id: R35 CA231620
Agency: NIAID NIH HHS, United States
Id: R01 AI044828
Agency: NIAID NIH HHS, United States
Id: R21 AI132960

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RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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