Uncovering New Molecular Drivers of Acute Lung Injury: Implications for Therapeutic Targeting

Acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), is a life-threatening syndrome triggered by systemic insults such as infection or trauma. It is characterized by intense pulmonary inflammation and increased vascular permeability that disrupt gas exchange. Despite decades of investigation, therapeutic strategies targeting aberrantly activated inflammatory cells, including corticosteroids, have produced inconsistent clinical benefits, underscoring the need for new mechanistic insights and therapeutic targets. Recent advances in innate immunology have begun to reveal pathways that regulate the dysregulated activation of phagocytes such as neutrophils and macrophages, highlighting previously unrecognized drivers of inflammatory tissue injury. In this lecture, I will discuss emerging mechanisms that amplify lung inflammation, with particular emphasis on inflammatory feedback loops between neutrophils and macrophages and on DNA-triggered inflammatory signaling pathways as potential drivers of organ injury, integrating insights from our recent studies.