RIPK3 Activation Leads to Cytokine Synthesis That Continues After Loss of Cell Membrane Integrity

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Aug 29

PMID 31461645

Citations 65

Authors

Susana L Orozco

Brian P Daniels

Nader Yatim

Michelle N Messmer

Giovanni Quarato

Haiyin Chen-Harris

Sean P Cullen

Annelise G Snyder

Pooja Ralli-Jain

Sharon Frase

Stephen W G Tait

Douglas R Green

Matthew L Albert

Andrew Oberst

Affiliations

Soon will be listed here.

Abstract

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.

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