基于细胞通讯探讨免疫细胞分化相关肺泡—毛细血管屏障损伤对脓毒性ARDS的影响  

Deciphering immune cell differentiation-induced alveolar-capillary barrier damage in septic ARDS via cell communication

作　　者：迟骋[1] 李雯莉[2] 陆玉成[3] 华实 Chi Cheng;Li Wenli;Lu yucheng;Hua Shi(Department of Emergency,Peking University People's Hospital,Beijing,100044,China;Emergency Trauma Center,The First Affiliated Hospital of Xinjiang Medical University,830011,China;Biobank,Linyi People’s Hospital,276000,China;Department of Neurosurgery,Linyi People’s Hospital,276000,China.)

机构地区：[1]北京大学人民医院急诊科,北京100044 [2]新疆医科大学第一附属医院急救·创伤中心急诊内科,乌鲁木齐830011 [3]临沂市人民医院生物样本库,临沂276000 [4]临沂市人民医院脑肿瘤与功能神经外科,临沂276000

出　　处：《中华急诊医学杂志》2024年第8期1117-1127,共11页Chinese Journal of Emergency Medicine

基　　金：山东省自然科学基金(ZR2023MH292);临沂市重点研发计划(2023YX0074)。

摘　　要：目的探讨免疫细胞分化对脓毒性ARDS肺泡-毛细血管屏障损伤的影响。方法基于转录组数据构建脓毒性ARDS的WGCNA网络,并筛选ARDS相关基因(ARDS-related genes,ARGs)。基于单细胞测序数据构建脓毒性ARDS分化轨迹和细胞通讯,并筛选免疫分化相关基因(immunodifferentiation-related genes,IDRGs)。Lasso回归分析构建ARDS的免疫相关风险评分(risk Score,RS)。ESTIMATE、CIBERSORT和ssGSEA评估免疫微环境。Metascape、GSVA和GO富集分析展示信号通路和生物学过程。结果免疫细胞、成纤维细胞和内皮细胞通过24条信号通路进行细胞通讯。由DSTN、SNRPA和FGL2组成的RS在正常、单纯脓毒症和脓毒性ARDS的患者中差异表达,涉及免疫细胞、内皮细胞和成纤维细胞的分化,影响脓毒性ARDS的免疫浸润和免疫功能。脓毒性ARDS相关免疫细胞包含记忆B细胞、浆细胞、CD8+T和M0。DSTN与M0负相关(r=-0.29,P<0.05),SNRPA与CD8+T正相关(r=0.28,P<0.05),FGL2与记忆B细胞正相关(r=0.32,P<0.05)。RS组间差异表达的免疫细胞包括CD4幼稚型T细胞、CD4记忆激活T细胞、调节T细胞、γ-δT细胞、M0、激活的树突状细胞。富集分析提示DSTN、SNRPA和FGL2的差异表达影响了免疫细胞的分化、免疫功能的激活、抗原的呈递,以及肌动蛋白丝的解聚/切断。结论DSTN、SNRPA和FGL2通过调控免疫细胞、成纤维细胞和内皮细胞的分化,影响脓毒性ARDS的免疫性肺泡-毛细血管屏障损伤,是预测脓毒性ARDS进展的潜在标志物。Objective To investigate the immune cell differentiation-induced alveolarcapillary barrier damage in septic ARDS via cell communication.Methods Construct septic ARDSrelated 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 naïve T cells,CD4 memory-activated T cells,regulatory T cells,γ-δT 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 immunerelated 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.

关 键 词：脓毒性ARDS 细胞分化 细胞通讯 DSTN SNRPA FGL2 

分 类 号：R459.7[医药卫生—急诊医学]