LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T cells.

ABSTRACT

BACKGROUND: The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms. METHODS: Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 180 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 180 on CD4+ T cell differentiation, proliferation, and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species, and ATP production measurements. The intracellular mechanism of LPG 180 in Tregs was investigated using small molecule inhibitors. RESULTS: The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 180 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG180 impaired naïve CD4+ T cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG180 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation. CONCLUSIONS: This study identifies that serum levels of LPG 180 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 180 impairs Treg function via the NAD+/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG180 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.