DAMP sensing and sterile inflammation: intracellular, intercellular and inter-organ pathways

Area of Science:

• Immunology
• Cell Biology
• Pathology

Background:

• Damage-associated molecular patterns (DAMPs) are released during cell death or damage, disrupting tissue homeostasis.
• Sensing DAMPs by innate immune receptors initiates inflammation, which can restore homeostasis or cause disease.
• Intracellular DAMP sensing is well-studied, but extracellular DAMPs also drive sterile inflammation.

Purpose of the Study:

• To summarize how DAMP-sensing receptors detect DAMPs from intracellular, intercellular, and distal sources.
• To explore the role of multi-level DAMP sensing in intercellular and trans-organ communication.
• To discuss targeting DAMPs or their receptors for treating inflammatory diseases.

Main Methods:

• Literature review of DAMP sensing mechanisms.
• Analysis of studies on sterile inflammation and innate immunity.
• Synthesis of findings on DAMP-mediated communication.

Main Results:

• DAMPs can originate from intracellular, neighboring, or distal sources to mediate sterile inflammation.
• DAMP sensing is critical for intercellular, trans-tissue, and trans-organ communication.
• Diverse DAMP-sensing receptors recognize these endogenous danger signals.

Conclusions:

• Multi-level DAMP sensing is a fundamental mechanism in sterile inflammation.
• Understanding DAMP-receptor interactions provides therapeutic avenues for inflammatory conditions.
• Targeting DAMP pathways holds promise for novel anti-inflammatory strategies.