세미나

Acute Lung Injury (ALI) and its severe form, Acute Respiratory Distress Syndrome (ARDS), represent a substantial clinical burden, further exacerbated by conditions such as COVID-19. While these syndromes serve as valuable models for studying complex inflammatory responses, the environmental factors that coordinate these processes remain incompletely understood.

In this study, we applied comprehensive multi-omics and biochemical approaches to uncover an unexpected role for neutrophil-derived itaconate as a key extracellular mediator that orchestrates sequential immune cell infiltration, including neutrophils, T cells, and monocytes. Mechanistically, extracellular itaconate metabolically facilitates Kdm5b-driven epigenetic remodeling at the promoters of Il6, Ccl5, and Cxcl10 in alveolar macrophages, thereby regulating immune cell recruitment.

Thus, our findings identify neutrophil-derived itaconate as a pivotal environmental signal that establishes tiered inflammatory responses and determines the overall magnitude of lung inflammation.

Finally, we will discuss the potential implications of this extracellular metabolic-epigenetic axis in the context of aging-associated alterations in inflammatory responses.