To identify and characterize immune checkpoint-related candidate key genes in pediatric asthma (PA) and their role in immune-metabolic dysregulation.
Key Findings:
HLA-DPA1 and HLA-DPB1 were identified as candidate key genes, significantly downregulated in PA, with high diagnostic value.
Downregulation correlated with attenuated antigen presentation and enhanced metabolic dysfunction.
Exploratory single-cell analysis revealed HLA-DPA1/DPB1 enrichment in macrophages, particularly in a Macro2 subset.
Pseudotime trajectory suggested a shift from immune-activated to metabolically stressed states.
Interpretation:
The study identifies HLA-DPA1 and HLA-DPB1 as key genes in childhood asthma, implicating them in immune-metabolic dysregulation and highlighting their role in macrophage heterogeneity.
Limitations:
Direct functional validation of HLA-DPA1 and HLA-DPB1's role in asthma is required to establish causality, which may limit the current findings.
Conclusion:
This research provides insights into innate immune circuits in childhood asthma and lays a foundation for potential molecular targets for future therapeutic strategies.
