Trained immunity induced by DAMPs and LAMPs in chronic inflammatory diseases

Abstract The immune system has traditionally been divided into innate and adaptive branches, with immunological memory considered a hallmark of adaptive immunity. However, recent studies reveal that innate immune cells can also exhibit memory-like properties, known as trained immunity. This phenomenon involves the long-term functional reprogramming of innate immune cells following exposure to exogenous or endogenous stimuli, mediated by epigenetic and metabolic changes. Trained immunity enhances responses to subsequent unrelated challenges and serves as a protective mechanism against reinfection. Nonetheless, it may also contribute to the development of chronic inflammatory diseases such as autoimmune disorders, allergies and atherosclerosis. Whereas much of the research has focused on pathogen-associated molecular patterns as inducers of trained immunity, emerging evidence highlights that sterile inflammation, driven by damage-associated molecular patterns and lifestyle-associated molecular patterns, can similarly induce this immune adaptation. Here we examine the molecular mechanisms underlying damage-associated molecular pattern- and lifestyle-associated molecular pattern-induced trained immunity and their roles in chronic inflammation. This Review also discusses central trained immunity, characterized by the durable reprogramming of hematopoietic stem and progenitor cells, and its implications in disease progression. Finally, potential therapeutic strategies targeting metabolic and epigenetic pathways are considered. Understanding noninfectious stimuli-induced trained immunity offers new insights into chronic inflammatory disease management.