Molecular Pathways Of Immune Suppression In Sepsis Based On Single Cell Transcriptional Sequencing

BackgroundSepsis is an acute and severe disease with high morbidity,mortality and high treatment cost.Immunosuppression is one of the characteristics of late sepsis,which is mainly related to the depletion of T lymphocyte number and the decrease of T lymphocyte receptor diversity.At present,there are many methods related to T lymphocytes to improve the immune suppression of sepsis,but the specific therapeutic mechanism and effect are not completely clear,and the mechanism of interaction between molecules and pathways that inhibit the expression of T cell receptor during sepsis immune suppression is still unknown.Therefore,in this study,single-cell transcriptome sequencing technology(scRNA-seq)was used to integrate multiple omics data,to preliminarily explore the regulatory mechanism of suppressed EXPRESSION of T cell receptor in sepsis at the molecular and pathway levels,and to provide a new strategy for immunotherapy of sepsis.ObjectiveMulti-omics data were integrated based on single-cell transcriptome sequencing technology(scRNA-seq)to explore the mechanism of interaction between molecules and pathways in the inhibition of T cell receptor expression in sepsis,and to preliminarily predict molecular biological targets for immunotherapy in sepsis.MethodsThis study will be of 4 patients with sepsis and 4 healthy controls of single-cell transcriptome sequencing data alignment,calibration,use R software(version 3.5.1)statistical analysis and visualization of the health control group with sepsis in the group the number of cells detected by statistics and clustering,based on differences in gene expression between cells abudance,cell clusters were isolated and cell types were inferred from classical single-cell reference data sets.To find out the types of T cells and T cell-specific expression cluster that are significantly related to immune suppression of sepsis,and compare the above information to the sepsis group and the healthy control group,and finally find out the specific corresponding cell cluster types of the healthy control group and the sepsis group.The differentially expressed signaling pathways in the healthy control group and the sepsis group were compared to further identify transcription molecules significantly differentially expressed in this biological signaling pathway,and further elaborate the interaction between the transcription-related molecules and biological signaling pathways in the state of immunosuppression of sepsis in the disease.ResultsIn this study,single-cell transcriptome sequencing was performed on blood samples(5mL)collected from 4 sepsis patients and 4 healthy controls,and comparative analysis was conducted based on multi-omics data integrated with single-cell transcriptome data,which was applied to study the immune suppression mechanism of sepsis at the molecular level.The results showed that:(1)Immunosuppression of sepsis was associated with a significant decrease in the number of T cells and the diversity of T cell receptor(TCR).(2)T cell receptor signaling pathway is inhibited in sepsis.(3)Nuclear transcription factor E2F2 was significantly active in patients with sepsis.(4)Transcription factor E2F2 may affect the immune response of T cells by blocking the T cell receptor signaling pathway and inhibiting the receptor expression of T cells,thus participating in the immunosuppression process of sepsis.ConclusionInhibition of E2F2 transcription can promote the transduction of T cell receptor signaling pathway,increase the expression of T cell surface receptors,and strengthen the immune response of T cells,which can improve the immunosuppression state of sepsis and provide potential molecular targets and new ideas for immunotherapy of sepsis in the future.