Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune resp...Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.展开更多
目的探讨慢性乙型肝炎患者外周血单个核细胞(PBMC)中转录因子ROG、GATA3和T-bet m RNA水平变化及意义。方法收集135例慢性乙型肝炎患者(轻度45例、中度42例、重度48例)和15例健康志愿者(正常对照组)的外周血,分离单个核细胞,提取总RNA,...目的探讨慢性乙型肝炎患者外周血单个核细胞(PBMC)中转录因子ROG、GATA3和T-bet m RNA水平变化及意义。方法收集135例慢性乙型肝炎患者(轻度45例、中度42例、重度48例)和15例健康志愿者(正常对照组)的外周血,分离单个核细胞,提取总RNA,用实时定量PCR的方法检测ROG、GATA3和T-bet m RNA水平。应用SPSS16.0软件进行统计分析。结果慢性乙型肝炎轻度、中度组和重度组患者外周血PBMCs中T-bet m RNA表达水平均明显高于健康对照组人群,组内比较差异均具有统计学意义(P<0.05)。慢性乙型肝炎重度组患者外周血PBMCs中ROG m RNA表达水平明显高于健康对照组人群、轻度组和中度组患者,差异均有统计学意义(P<0.05)。而轻度组、中度组患者和健康对照组比较差异均无统计学意义(P>0.05)。慢性乙型肝炎中度组和重度组患者外周血PBMCs中GATA3 m RNA表达水平明显高于健康对照组人群和轻度组患者,差异均具有统计学意义(P<0.05);而轻度组和健康对照、中度组患者和重度组比较差异均无统计学意义(P>0.05)。慢性乙型肝炎轻度、中度组和重度组患者T-bet/GATA3比值明显高于健康对照组人群,差异均具有统计学意义(P<0.05);但3组之间比较差异无统计学意义(P>0.05)。ROG表达水平与GATA3和T-bet/GATA3比值均无相关性(P>0.05)。结论 ROG、GATA3和T-bet在慢性乙型肝炎患者外周血PBMCs中表达水平上调,并参与疾病的发生和疾病进展。ROG在纠正和维持Th1/Th2的新平衡状态过程中起重要作用。展开更多
基金financially supported by the Biological Breeding-National Science and Technology Major Project(No.2023ZD0407106)National Key R&D Program of China(No.2023YFD1300400)Biological Breeding-National Science and Technology Major Project,No.2023ZD0407106,Kai Xing。
文摘Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.
文摘目的探讨慢性乙型肝炎患者外周血单个核细胞(PBMC)中转录因子ROG、GATA3和T-bet m RNA水平变化及意义。方法收集135例慢性乙型肝炎患者(轻度45例、中度42例、重度48例)和15例健康志愿者(正常对照组)的外周血,分离单个核细胞,提取总RNA,用实时定量PCR的方法检测ROG、GATA3和T-bet m RNA水平。应用SPSS16.0软件进行统计分析。结果慢性乙型肝炎轻度、中度组和重度组患者外周血PBMCs中T-bet m RNA表达水平均明显高于健康对照组人群,组内比较差异均具有统计学意义(P<0.05)。慢性乙型肝炎重度组患者外周血PBMCs中ROG m RNA表达水平明显高于健康对照组人群、轻度组和中度组患者,差异均有统计学意义(P<0.05)。而轻度组、中度组患者和健康对照组比较差异均无统计学意义(P>0.05)。慢性乙型肝炎中度组和重度组患者外周血PBMCs中GATA3 m RNA表达水平明显高于健康对照组人群和轻度组患者,差异均具有统计学意义(P<0.05);而轻度组和健康对照、中度组患者和重度组比较差异均无统计学意义(P>0.05)。慢性乙型肝炎轻度、中度组和重度组患者T-bet/GATA3比值明显高于健康对照组人群,差异均具有统计学意义(P<0.05);但3组之间比较差异无统计学意义(P>0.05)。ROG表达水平与GATA3和T-bet/GATA3比值均无相关性(P>0.05)。结论 ROG、GATA3和T-bet在慢性乙型肝炎患者外周血PBMCs中表达水平上调,并参与疾病的发生和疾病进展。ROG在纠正和维持Th1/Th2的新平衡状态过程中起重要作用。