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Published on: January 20, 2023
DAMPs in the immunogenicity of cell death
Ruochan Chen1, Ju Zou1, Jiao Liu2
1Department of Infectious Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, China; Hunan Key Laboratory of Viral Hepatitis, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Abstract:
Damage-associated molecular patterns (DAMPs) are endogenous molecules-such as proteins, lipids, and nucleic acids-released or exposed during cellular injury or stress, which shape immune responses by engaging danger sensors on the cell surface or within the cell interior. Recent advances have elucidated molecular links between distinct cell death pathways-apoptosis, necroptosis, pyroptosis, and ferroptosis-and DAMP release, emphasizing how biochemical features (e.g., posttranslational modifications) and temporal dynamics influence immunogenic versus tolerogenic outcomes. Here, we summarize these mechanisms, including both immunostimulatory and immunosuppressive DAMPs, and review key DAMP receptors-such as TLRs, NLRs, cGAS, and advanced glycosylation end-product-specific receptor (AGER)/RAGE-along with their downstream signaling cascades. Finally, we highlight emerging strategies to modulate DAMP signaling for cancer immunotherapy and the treatment of inflammatory diseases.
Insights
Damage-associated molecular patterns (DAMPs) are released during cell injury and influence immune responses. Understanding DAMPs and their receptors offers new strategies for cancer immunotherapy and treating inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury.
- These molecules engage danger sensors, shaping immune responses towards either immunostimulatory or tolerogenic outcomes.
- Recent research links specific cell death pathways (apoptosis, necroptosis, pyroptosis, ferroptosis) to DAMP release.
Purpose of the Study:
- To summarize mechanisms of DAMP release and their impact on immune responses.
- To review key DAMP receptors and their downstream signaling pathways.
- To highlight emerging strategies for modulating DAMP signaling in disease treatment.
Main Methods:
- Review of current literature on DAMPs, cell death pathways, and immune signaling.
- Analysis of molecular links between cell death and DAMP release.
- Identification of key DAMP receptors and their associated signaling cascades.
Main Results:
- DAMPs can elicit both immunostimulatory and immunosuppressive immune responses.
- Biochemical features and temporal dynamics of DAMP release influence immune outcomes.
- Key DAMP receptors include TLRs, NLRs, cGAS, and AGER/RAGE.
Conclusions:
- Modulating DAMP signaling presents a promising therapeutic avenue for cancer immunotherapy.
- Targeting DAMP pathways may offer new treatments for inflammatory diseases.
- Further research into DAMP mechanisms can advance our understanding of immune regulation.
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