Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia.

Background. Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4+ T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with...

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Publicado en:BioMed Research International pp. 1 - 12
Autores principales: Tang, Meiwen, Cheng, Luya, Li, Feng, Wu, Boting, Chen, Pu, Zhan, Yanxia, Hua, Fanli, Min, Zhihui, Ke, Yang, Liu, Chanjuan, Yuan, Ling, Sun, Lihua, Chen, Hao, Ji, Lili, Cheng, Yunfeng
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 7/10/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 7/10/2019
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2019/1050285
        137409562
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        atl: Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia.
      aug:
        au:
          Tang, Meiwen
          Cheng, Luya
          Li, Feng
          Wu, Boting
          Chen, Pu
          Zhan, Yanxia
          Hua, Fanli
          Min, Zhihui
          Ke, Yang
          Liu, Chanjuan
          Yuan, Ling
          Sun, Lihua
          Chen, Hao
          Ji, Lili
          Cheng, Yunfeng
        affil: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, China
      sug:
        subj:
          T Lymphocytes Metabolism
          Thrombocytopenia Physiopathology
          Proteins
          Transcription Factors Metabolism
          Immunosuppression
          Autoimmune Diseases Physiopathology
          Human
          Flow Cytometry
          Interleukins
          Leukocytes, Mononuclear
          DNA
          RNA, Messenger
          Autoimmune Diseases Immunology
      ab: Background. Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4+ T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP. Methods. Treg and Teff cells were isolated from PBMCs of newly diagnosed ITP patients. The percentages of CD4+CD25hiFoxp3+Treg cells and the CD3+CD4+IL-17+Th17 cells were detected by flow cytometry. After being cultured, the supernatants of Tregs were collected for IL-10 concentration test. The IRF4 levels of Tregs were measured. Teffs were cultured alone or with Tregs for 24 hours. Then the supernatants were collected for IL-17 concentration test. The binding intensity of IRF4 to the gene IL-10 in Treg cells was detected by ChIP-qPCR. Metabolic assays for Teffs and Tregs were performed with Agilent Seahorse XF96 Analyzer. Results. The secretion of IL-10 by Tregs was decreased in ITP patients. The intensity of IRF4 binding to IL-10 DNA of Tregs in patients was higher than that of normal controls and Teffs in ITP patients. The expressions of IRF4 of Tregs in ITP patients were remarkably lower than that of healthy controls. The percentage of Th17 cells in healthy controls was significantly increased after IRF4 mRNA silencing. Abnormal metabolism of Treg and Teff cells was found in ITP patients. Conclusion. The skewed ratio of Th17/Treg cells and dysfunction of Treg cells in newly diagnosed ITP patients was at least partly caused by IRF4 dysfunction. The underlying mechanism might be the impact of IRF4 on the metabolism of Treg and Teff cells.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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