Oxidized phospholipid damage signals as modulators of immunity

Damage-associated molecular patterns (DAMPs) are self-derived molecules released during tissue damage that influence immune responses. Phospholipids, essential to cell membranes and lung surfactants, become oxidized under conditions of cellular stress, forming oxidized phospholipids. Unlike their unoxidized counterparts, oxidized phospholipids function as DAMPs and engage pattern recognition receptors (PRRs) on innate immune cells, activating signalling pathways that regulate immune responses. This activity alters innate immune cells, which in turn modulate the adaptive immune response, ultimately contributing to the pathogenesis of disease. Traditionally considered pro-inflammatory, recent studies reveal a more nuanced role for these lipids, with their effects on immune cells being context dependent. This review examines the mechanisms behind the generation of oxidized phospholipids and their induction in disease. We focus on recent studies that clarify how these lipids affect innate immune cells, leading to downstream effects on adaptive immunity, as well as their direct influence on adaptive immune cells. Finally, we explore therapeutic strategies targeting oxidized phospholipids to regulate immunity, offering insights into their broader role in immune regulation and potential applications in disease prevention.