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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Forkhead transcription factor FOXO FOXO 3a mediates interferon‐ γ γ ‐induced MHC II MHC II transcription in macrophages
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Forkhead transcription factor FOXO FOXO 3a mediates interferon‐ γ γ ‐induced MHC II MHC II transcription in macrophages

机译:FORKHEAD转录因子FOXO FOXO 3A介导干扰素-γγ-诱导巨噬细胞中的MHC II MHC II转录

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摘要

Summary Macrophages are professional antigen‐presenting cells relying on the expression of class II major histocompatibility complex ( MHC II ) genes. Interferon‐ γ ( IFN ‐ γ ) activates MHC II transcription via the assembly of an enhanceosome centred on class II trans‐activator ( CIITA ). In the present study, we investigated the role of the forkhead transcription factor FOXO 3a in IFN ‐ γ ‐induced MHC II transcription in macrophages. Knockdown of FOXO 3a, but not FOXO 1 or FOXO 4, diminished IFN ‐ γ ‐induced MHC II expression in RAW cells. On the contrary, over‐expression of FOXO 3a, but neither FOXO 1 nor FOXO 4, enhanced CIITA ‐mediated trans‐activation of the MHC II promoter. IFN ‐ γ treatment promoted the recruitment of FOXO 3a to the MHC II promoter. Co‐immunoprecipitation and RE ‐Ch IP assays showed that FOXO 3a was a component of the MHC II enhanceosome forming interactions with CIITA , RFX 5, RFXB and RFXAP . FOXO 3a contributed to MHC II transcription by altering histone modifications surrounding the MHC II promoter. Of interest, FOXO 3a was recruited to the type IV CIITA promoter and directly activated CIITA transcription by interacting with signal transducer of activation and transcription 1 in response to IFN ‐ γ stimulation. In conclusion, our data unveil a novel role for FOXO 3a in the regulation of MHC II transcription in macrophages.
机译:发明内容巨噬细胞是专业的抗原呈递细胞,依赖于II类主要组织相容性复合物(MHC II)基因的表达。干扰素-γ(IFN-γ)通过集中在II类转移剂(CIita)的增强体组装激活MHC II转录。在本研究中,我们研究了FORKHEAD转录因子FOXO 3a在巨噬细胞IFN-γ-ind引出的MHC II转录中的作用。 FOXO 3A的敲低,但不是FOXO 1或FOXO 4,IFN - γ-诱导的MHC II在原料细胞中表达。相反,FOXO 3A的过度表达,但既不是FOXO 1也不是FOXO 4,增强了MHC II启动子的CIITA介导的泛激活。 IFN - γ治疗促进FOXO 3a募集到MHC II启动子。共免疫沉淀和RE -CH IP测定表明FOXO 3A是MHC II的组分,其增强与CIITA,RFX 5,RFXB和RFXAP的相互作用。通过改变MHC II启动子周围的组蛋白修饰,FOXO 3A导致MHC II转录。感兴趣的是,通过与IFN - γ刺激的信号传感器相互作用,募集到IV型Ciita启动子和直接激活的Ciita转录,并响应IFN - γ刺激。总之,我们的数据揭示了FOXO 3a在巨噬细胞MHC II转录的调节中的一种新颖作用。

著录项

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  • 作者单位

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    Department of PathologyNanjing Drum Tower Hospital Affiliated with Nanjing University School of;

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    The Laboratory Centre for Basic Medical SciencesNanjing Medical UniversityNanjing China;

    Department of GeriatricsThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing China;

    Institute of Biomedical ResearchLiaocheng UniversityLiaocheng China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    epigenetics; FOXO; macrophage; transcriptional regulation;

    机译:表观遗传学;FOXO;巨噬细胞;转录规则;

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