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中文摘要
翻译
先天淋巴细胞、单核细胞、调节性T细胞(Tregs)和调节性B细胞(Bregs)通过分泌IL-10和IL-35抑制CNS自身免疫性疾病,如葡萄膜炎或多发性硬化症。这些免疫抑制因子的活性是通过激活JAK/STAT信号通路介导的,并受到严格的调控。在这项研究中,我们试图确定体内产生这两种细胞因子的主要细胞类型,并描述调节其产生的机制。
英文摘要
Innate lymphocytes, monocytes, regulatory T cells (Tregs) and regulatory B cells (Bregs) suppress CNS autoimmune diseases such as Uveitis or Multiple Sclerosis by secreting IL-10 and IL-35. The activities of these immune suppressive cytokines are mediated through activation of JAK/STAT signaling pathway and are under stringent regulation. In this study, we sought to identify major cell types that produce both cytokines in-vivo and to characterize mechanisms that regulate their production. Compared to innate or Tregs we found that Bregs are the major producers of IL-35 and IL-10 in vivo during ocular inflammatory diseases. We also found that BATF, IFN regulatory factor (IRF)-4, and IRF-8 transcription factors are recruited and bind to AP1-IRF-composite elements (AICEs) of il12a, ebi3, and/or il10 loci, suggesting that these transcription factors regulate IL-10 and IL-35 expression by activated B cells. We also found that STAT3-dependent and independent pathways control ocular inflammation. These studies suggest that targeting STAT3 pathways and the BATF/IRF-4/IRF-8 axis can be exploited therapeutically to regulate physiological levels of IL-10/IL-35-Bregs and ocular inflammation.
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Interferon-inducible Transcription Factors: Roles In Ocu
  • 批准号:
    6507394
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Charles E Egwuagu
  • 依托单位:
INTERFERON INDUCIBLE TRANSCRIPTION FACTORS: ROLES IN OCU
  • 批准号:
    6414669
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Charles E Egwuagu
  • 依托单位:
Role of IL-12 family cytokines in human autoimmune Uveit
  • 批准号:
    7321809
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Charles E Egwuagu
  • 依托单位:
Development of dendritic cell vaccine against uveitis
  • 批准号:
    6968529
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Charles E Egwuagu
  • 依托单位: