Deciphering immune cell differentiation-induced alveolar-capillary barrier damage in septic ARDS via cell communication
Objective To investigate the immune cell differentiation-induced alveolar-capillary barrier damage in septic ARDS via cell communication.Methods Construct septic ARDS-related WGCNA network based on transcriptomic data and identify ARDS-related genes(ARGs).Constructed septic ARDS differentiation trajectories,predicted cellular communication,and screened immunodifferentiation-related genes(IDRGs)based on single-cell sequencing data.Lasso regression analysis establish immune-related RS of ARDS.ESTIMATE,CIBERSORT,and ssGSEA assessed the immune microenvironment.Metascape,GSVA and GO enrichment analyses demonstrated RS-related signaling pathways and biological processes.Results Cell communication between immune cells and fibroblasts/endothelial cells involves 22 signaling pathways.RS containing DSTN,SNRPA,and FGL2 were differentially expressed in healthy,sepsis,and septic ARDS patients,affecting the differentiation of immune cells,endothelial cells,and fibroblasts,and regulating the infiltration of the immune cells and immune functions.The characteristic immune cells in septic ARDS included memory B cells,plasma cells,CD8+T,and M0;DSTN was negatively correlated with M0(r=-0.29,P＜0.05),SNRPA was positively correlated with CD8+T(r=0.28,P＜0.05),and FGL2 was positively correlated with memory B cells(r=0.32,P＜0.05).The immune cells that were differentially expressed between RS groups,including CD4 naive T cells,CD4 memory-activated T cells,regulatory T cells,γ-δ T cells,M0,and activated dendritic cells.Enrichment analysis indicated the differential expression of DSTN,SNRPA,and FGL2 affected the differentiation of immune cells,the activation of immune functions,the presentation of antigens,and the depolymerization/cutting of actin filaments.Conclusions DSTN,SNRPA,and FGL2 affect immune-related alveolar-capillary barrier damage in septic ARDS by regulating the differentiation of immune cells,fibroblasts,and endothelial cells,and are potential biomarkers for predicting the progression of septic ARDS.
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