Choline supplementation protects against sepsis-induced lung injury, potentially through suppression of Prtn3-associated monocyte activation.

Objective: Choline supplementation has been implicated in the regulation of inflammation and immune responses. This study aimed to investigate the protective effects of choline supplementation in sepsis-induced lung injury (SLI) and to elucidate the underlying mechanisms. Methods: SLI was induced in mice via cecal ligation and puncture (CLP). Serum choline levels were measured, and choline supplementation effects were evaluated Results: Compared with Sham controls, SLI mice exhibited significantly decreased serum choline levels. The SLI mouse model exhibited typical pathological features, including pulmonary hemorrhage, interstitial edema, alveolar wall thickening, elevated inflammatory cytokines, and increased lung injury scores, all of which were significantly alleviated by choline supplementation. Multi-omics analyses identified Prtn3 as a potential target associated with the protective effects of choline. Single-cell analysis suggested that Prtn3 is predominantly expressed in monocyte/macrophage populations. Conclusion: Choline supplementation protects against SLI by suppressing monocyte inflammatory activation, at least in part through inhibition of the Prtn3-dependent NF-κB signaling pathway. These findings suggest that targeting the choline-Prtn3-NF-κB axis may represent a potential therapeutic strategy for sepsis-associated lung injury.