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Origin and Consequences of Necroinflammation.

Maysa Sarhan¹, Walter G Land¹, Wulf Tonnus¹

¹Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna , Vienna , Austria ; INSERM UMR_S 1109, Laboratory of Excellence Transplantex, University of Strasbourg , Strasbourg , France ; German Academy of Transplantation Medicine, Munich , Germany ; and Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden , Dresden , Germany.

Physiological Reviews

|February 22, 2018

Summary

Regulated necrosis (RN) pathways, including necroptosis, ferroptosis, and pyroptosis, trigger immune responses by releasing damage-associated molecular patterns (DAMPs). Understanding these pathways and DAMPs aids in preventing necroinflammation and modulating regeneration.

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Area of Science:

Immunology
Cell Biology
Molecular Biology

Background:

Necrotic cell death releases immunogenic molecules, activating the immune system.
Regulated necrosis (RN) is a genetically determined process that can be pharmacologically targeted.
Multiple conserved RN pathways (necroptosis, ferroptosis, pyroptosis) differ in immunogenicity.

Purpose of the Study:

To review signaling pathways of necrotic cell death and their role in necroinflammation.
To explore the immunogenicity and immune-modulating functions of damage-associated molecular patterns (DAMPs).
To introduce a novel classification of DAMPs for better understanding of RN pathways in disease.

Main Methods:

Literature review of signaling pathways in regulated necrosis.
Analysis of damage-associated molecular patterns (DAMPs) released during necrotic cell death.
Examination of cytokine/chemokine expression and maturation in RN pathways.

Main Results:

All RN pathways release DAMPs, but specific pathways actively regulate the immune system via cytokines/chemokines.
DAMPs modulate immune responses and influence tissue regeneration processes.
Distinct signatures of necroinflammation can characterize specific RN pathways.

Conclusions:

Necroinflammation arises from regulated necrosis pathways, each with unique DAMP-related immune signaling.
Targeting RN pathways and understanding DAMPs offers therapeutic potential for inflammatory diseases.
A novel DAMP classification system can elucidate the contribution of each RN pathway to various conditions.