Identification of key immune genes for sepsis-induced ARDS based on bioinformatics analysis

Abstract

ABSTRACT Regarding the extremely high mortality caused by sepsis-induced acute respiratory distress syndrome (ARDS), it is urgent to develop new biomarkers of sepsis-induced ARDS for treatment. Here, 532 differential expression genes (DEGs) related to sepsis and 433 DEGs related to sepsis-induced ARDS were screened in the GSE32707 dataset. Compared with sepsis samples, sepsis ARDS samples showed a higher infiltration of activated memory CD4 T cells and naive B cells, but a relatively lower infiltration of CD8 T cells. The pink and green modules which are significantly associated with sepsis-induced ARDS were then screened through co-expression network analysis. Differentially up-regulated GYPE and aberrantly down-regulated HSPB1, were subsequently found in the pink module of ARDS. CD81 and RPL22, two differentially low-expressed genes peculiar to ARDS, were identified in the green module. The function of CD81 was verified at the cellular level, and it was found that the up-regulation of CD81 in A549 could alleviate the LPS-induced injury of A549 cells. More importantly, the overexpressed CD81 can also increase the content of CD4+ CD25+ Foxp3+ Treg in Jurkat cells, and after the co-culture of overexpressed CD81 Jurkat cells with LPS treatment A549 cells, the LPS-induced lung epithelial cell damage can be improved. Overall, four new plasma biomarker candidates were found in sepsis-induced ARDS, and we verified that CD81 may play critical roles in the biological and immunological processes of sepsis-induced ARDS.