摘要
目的:探讨胆道闭锁(BA)肝脏不同病理分期的免疫微环境差异。方法:GEO数据库收集包含BA肝活检病理信息的芯片数据,ImmPort数据库下载免疫相关基因集,采用生物信息学方法分析BA发展中的免疫相关基因、浸润免疫细胞及激活通路。结果:通过差异分析得到13个免疫相关基因,其中MMP9、IL1RL1、MPO、CCL20、PTX3、HSPA6、CTSG和RNASE3主要在炎症组中高表达,RASGRP1、SEMA6A、CXCL11、GREM1和CD8A在纤维化组中高表达。ImmuCellAI分析提示肝纤维化组中nTreg及iTreg呈高表达,NKT细胞及中性粒细胞在炎症组中高表达。GSEA分析显示炎症组激活代谢及细胞信号传导相关分子途径,纤维化组激活主要是细胞基质及T细胞介导的适应性免疫应答相关分子途径。结论:免疫微环境在BA发生和发展中起重要作用,有助于阐明BA发病机制及为BA治疗提供新的方向。
Objective:To investigate difference of immune microenvironment in different pathological stages of liver in biliary atresia(BA).Methods:Chip data containing BA liver biopsy pathological information was collected from GEO database and immunerelated gene set was downloaded from ImmPort database.Immune-related genes,infiltrated immune cells and activation pathways in development of BA were analyzed by bioinformatics.Results:Thirteen immune-related genes were obtained by differential analysis,among which MMP9,IL1RL1,MPO,CCL20,PTX3,HSPA6,CTSG and RNASE3 were mainly highly expressed in inflammatory group,while RASGRP1,SEMA6A,CXCL11,GREM1 and CD8A were highly expressed in fibrotic group.ImmuCellAI analysis suggested that nTreg and iTreg cells were highly expressed in fibrotic group,while NKT cells and neutrophil cells were highly expressed in inflammatory group.GSEA analysis showed that inflammatory group activated molecular pathways related to metabolism and cell signal transduction,while fibrosis group activated mainly pathways related to cell matrix and T-cell-mediated adaptive immune response.Conclusion:Immune microenvironment plays an important role in occurrence and development of BA,which is helpful to elucidate pathogenesis of BA and provide a new direction for BA treatment.
作者
张昊东
康权(指导)
ZHANG Haodong;KANG Quan(Department of General Surgery,Yuzhong District,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Engineering Research Center of Stem Cell Therapy,Chongqing 400014,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2022年第6期656-660,共5页
Chinese Journal of Immunology
基金
重庆市自然科学基金面上项目(cstc2020jcyj-msxmX0113)。
关键词
胆道闭锁
免疫微环境
生物信息学
Biliary atresia
Immune microenvironment
Bioinformatics
