山西医科大学学报2025，Vol.56Issue(7)：758-766,9.DOI:10.13753/j.issn.1007-6611.2025.07.005
基于转录组学与细胞模型的天然免疫网络昼夜节律特性研究
Research on circadian rhythm characteristics of innate immune network based on transcriptomics and cell models
摘要
Abstract
Objective To systematically analyze the global rhythmic characteristics of the innate immune network and explore the fea-sibility of immune intervention based on the circadian rhythm system.Methods The transcriptome datasets from the two major pub-lic databases,GEO and GTEx,were integrated to systematically dissect the circadian oscillation characteristics of 54 core genes in four innate immune pathways.A circadian rhythm model of 293T cells was established by dexamethasone synchronization treatment to verify the rhythmic characteristics of gene expression and immune response intensity in the retinoic acid-inducible gene Ⅰ(RIG-Ⅰ)re-ceptor pathway.293T cells were respectively treated with the key circadian rhythm system gene REV-ERBα inhibitor SR8278 and the gene CLOCK inhibitor CLK8 to investigate the impact of interfering with the circadian rhythm system on innate immune responses.Results The results of transcriptome data analysis showed that among the 54 key genes of innate immunity,30 genes including IRAK1 exhibited circadian oscillation characteristics.Among them,the molecules such as TBK1 kinase and NF-κB subunit RELA showed significant and stable rhythmic expression in at least two sample types including U2OS cells and vaginal tissues(P＜0.05).In the circadian rhythm model based on 293T cells,the expressions of IFIH1,TBK1,IRAK1,RELA and IRF3 genes in the RIG-Ⅰ sig-naling pathway showed significant circadian rhythm changes,and the intensity of the immune response also presented significant circa-dian rhythm characteristics.The expression levels of ISG15,INFβ,ISG56 and CCL5 at ZT24 were significantly lower than that at ZT12(P＜0.05).The results of the circadian rhythm intervention experiments showed that compared with CLK8 treatment group,the expression levels of the natural immune effector molecule genes ISG15,INFβ,ISG56 and CCL5 in 293T cells increased by more than 30％in SR8278 treatment group(P＜0.05).Conclusion The expression of core genes in the innate immune network shows significant circadian oscillation rhythms,and activating the circadian rhythm system can effectively enhance the immune response level.It is sci-entifically feasible to carry out immune intervention based on the circadian rhythm system.关键词
昼夜节律系统/天然免疫信号通路/转录组分析/时间节律调控/细胞模型/"时间精准化"治疗Key words
circadian rhythm system/innate immune signaling pathway/transcriptome analysis/temporal rhythm regulation/cell model/"time-precise"treatment分类
医药卫生引用本文复制引用
王建新,于明航,刘晓蕊,王玺..基于转录组学与细胞模型的天然免疫网络昼夜节律特性研究[J].山西医科大学学报,2025,56(7):758-766,9.基金项目
国家自然科学基金项目(81972652,32270635) （81972652,32270635）
北京市自然科学基金项目(7232082,5254029) （7232082,5254029）
首都医科大学培育基金项目(PYZ24165) （PYZ24165）
量子传感与精密测量山西省重点实验室开放基金项目(201905D121001005) （201905D121001005）
首都医科大学附属北京地坛医院院内科研基金项目(DTQL-202405) （DTQL-202405）
