Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released from host cells as a result of cell death or damage. The release of DAMPs in tissues is associated with loss of tissue homeostasis. Sensing of DAMPs by innate immune receptors triggers inflammation, which can be beneficial in initiating the processes that restore tissue homeostasis but can also drive inflammatory diseases. In recent years, the sensing of intracellular DAMPs has received extensive attention in the field of sterile inflammation. However, emerging studies have shown that DAMPs that originate from neighbouring cells, and even from distal tissues or organs, also mediate sterile inflammatory responses. This multi-level sensing of DAMPs is crucial for intercellular, trans-tissue and trans-organ communication. Here, we summarize how DAMP-sensing receptors detect DAMPs from intracellular, intercellular or distal tissue and organ sources to mediate sterile inflammation. We also discuss the possibility of targeting DAMPs or their corresponding receptors to treat inflammatory diseases.

损伤相关分子模式 (DAMP) 是由于细胞死亡或损伤而从宿主细胞中释放的内源性分子。组织中 DAMP 的释放与组织稳态的丧失有关。先天免疫受体对 DAMP 的感知会引发炎症，这有利于启动恢复组织稳态的过程，但也可能引发炎症性疾病。近年来，细胞内 DAMP 的传感在无菌炎症领域受到广泛关注。然而，新兴研究表明，源自邻近细胞甚至远端组织或器官的 DAMP 也能介导无菌炎症反应。这种 DAMP 的多层次传感对于细胞间、跨组织和跨器官通讯至关重要。在这里，我们总结了 DAMP 感应受体如何检测来自细胞内、细胞间或远端组织和器官来源的 DAMP 来介导无菌炎症。我们还讨论了靶向 DAMP 或其相应受体来治疗炎症性疾病的可能性。