Regulated cell death and inflammation: an auto-amplification loop causes organ failure

Area of Science:

• Immunology
• Cell Biology
• Pathophysiology

Background:

• Regulated cell death (RCD) can be immunologically silent or immunogenic.
• Parenchymal cell RCD can release damage-associated molecular patterns (DAMPs), initiating inflammation and further RCD.
• A feedback loop exists where RCD and inflammation mutually amplify, leading to exaggerated cell death.

Purpose of the Study:

• To propose that the crosstalk between pro-inflammatory and RCD pathways is pathologically relevant.
• To highlight the role of this crosstalk in solid organ failure, transplantation, and cancer.
• To advocate for therapeutic strategies targeting this RCD-inflammation circuit.

Main Methods:

• This is an Opinion article, presenting a conceptual framework.
• Literature review and synthesis of existing knowledge on RCD and inflammation.
• Discussion of pathophysiological implications and therapeutic considerations.

Main Results:

• The interplay between RCD and inflammation creates an auto-amplification loop.
• This crosstalk is implicated in the pathogenesis of solid organ failure.
• The RCD-inflammation circuit is relevant in transplantation and cancer biology.

Conclusions:

• Clinicians should consider targeting the RCD-inflammation circuit.
• Immunosuppressive treatments can disrupt this circuit.
• Interfering with RCD pathways represents a neglected but potentially valuable therapeutic option.