Viral sensor IFIH1 promotes SLE through an altered interferon program

病毒传感器 IFIH1 通过改变干扰素程序促进 SLE

基本信息

  • 批准号:
    10090982
  • 负责人:
  • 金额:
    $ 34.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-02-05 至 2026-01-31
  • 项目状态:
    未结题

项目摘要

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from an interactive web of genetic and environmental factors. SLE is associated with elevated levels of type I interferons (IFN I) and viral infections. Single nucleotide polymorphisms (SNPs) in the innate immune signaling pathway have been linked to an increased risk for SLE by genome wide association studies. One common SNP that is strongly associated with SLE is located in the viral dsRNA sensor, IFIH1 (rs1990760), which results in an amino acid change (A946T). The precise roles of the IFIHI T946 variant in SLE pathogenesis remain unclear. Recently, we showed that a knock- in mouse model expressing the IFIH1 variant (IFIH1T946; Ifih1R) displays heightened basal IFN I expression and a signature of interferon-stimulated genes (ISGs) in immune cells. This low grade interferonopathy correlates with increased persistence of anti-nuclear autoantibodies in an induced SLE model. Therefore, the Ifih1R model provides a unique opportunity to determine how the IFIH1T946 variant primes immune cells for elevated responses that promote autoimmunity. Herein, we will focus on two aims: 1) elucidating the role of pDCs in the elevated IFN signature in Ifih1R mice, and 2) determining how IFIH1R alters CD4+ T cell effector function and associated cellular metabolic remodeling that lead to SLE pathogenesis. Successful completion of these aims will elucidate transcriptional and metabolic mechanisms by which IFIH1R primes pDCs and CD4+ T cells to promote SLE pathogenesis. The information gained will help guide therapeutic approaches based on alterations in metabolic pathways in SLE and other autoimmune diseases.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,由遗传和神经网络相互作用引起

项目成果

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Jacquelyn Gorman其他文献

Jacquelyn Gorman的其他文献

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{{ truncateString('Jacquelyn Gorman', 18)}}的其他基金

Viral sensor IFIH1 promotes SLE through an altered interferon program
病毒传感器 IFIH1 通过改变干扰素程序促进 SLE
  • 批准号:
    10571906
  • 财政年份:
    2021
  • 资助金额:
    $ 34.96万
  • 项目类别:
Viral sensor IFIH1 promotes SLE through an altered interferon program
病毒传感器 IFIH1 通过改变干扰素程序促进 SLE
  • 批准号:
    10339354
  • 财政年份:
    2021
  • 资助金额:
    $ 34.96万
  • 项目类别:

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