Unraveling the role of HLA-B51/ERAP1 in Behcet's eye disease

揭示 HLA-B51/ERAP1 在白塞氏眼病中的作用

基本信息

项目摘要

ABSTRACT / PROJECT SUMMARY HLA-B*51 in epistasis with the ERAP1 haplotype Hap10 confers the strongest currently known risk for Behcet’s Disease (BD) and Behcet’s Eye Disease (BED), but the consequences of this relationship for immune-phenotype, clonality, and function, are entirely unknown. The main objective of this application is to identify these consequences. This is in line with our long-term goal to find, comprehend, and correct aberrancies in immune pathways that drive Behcet’s Eye Disease (BED). Based on our preliminary studies we propose as our central hypothesis that ERAP1 Hap10 shapes immune responses in HLA-B*51+ BED through the activation of clonal CD8 T and NKT effector cell populations that drive the disease. We follow the rationale that elucidation of the biological consequences of HLA-B51/ERAP1 Hap10 will promote a mechanistic understanding of BED in affected carriers, and therefore enable targeted therapy design. We will test our central hypothesis in two specific aims: 1) Through the determination of immune phenotypes linked to HLA-B*51+/ERAP1 Hap10 BED, combining access to unique patient cohorts of our own and those of our international collaborators with large-scale flow cytometric analyses using computational tools we have developed. 2) Through the identification of clonal effector responses and function in BED patients using single cell-transcriptomics and methods of T cell cloning we have established. Meeting the objective of this proposal will generate knowledge providing scientific rationale for the design of targeted therapies for BED, which is one of the most devastating forms of non-infectious uveitis with significant prevalence in large parts of the world. We expect additional positive impact by cross-fertilizing research of other HLA-I/ERAP-related diseases including HLA-B27-associated uveitis and spondylitis, Birdshot’s choroidopathy, psoriasis-associated conditions, and inflammatory bowel disease (IBD).
摘要/项目总结

项目成果

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Johannes Nowatzky其他文献

Johannes Nowatzky的其他文献

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{{ truncateString('Johannes Nowatzky', 18)}}的其他基金

Modulation of immunodominance in HLA class I associated uveitides
HLA I 类相关葡萄膜的免疫优势调节
  • 批准号:
    10557821
  • 财政年份:
    2022
  • 资助金额:
    $ 41.1万
  • 项目类别:
Modulation of immunodominance in HLA class I associated uveitides
HLA I 类相关葡萄膜的免疫优势调节
  • 批准号:
    10345839
  • 财政年份:
    2022
  • 资助金额:
    $ 41.1万
  • 项目类别:
Unraveling the role of HLA-B51/ERAP1 in Behcet's eye disease
揭示 HLA-B51/ERAP1 在白塞氏眼病中的作用
  • 批准号:
    10534165
  • 财政年份:
    2021
  • 资助金额:
    $ 41.1万
  • 项目类别:
Harnessing monoclonal Treg for the treatment of autoimmune uveitis
利用单克隆 Treg 治疗自身免疫性葡萄膜炎
  • 批准号:
    8869794
  • 财政年份:
    2015
  • 资助金额:
    $ 41.1万
  • 项目类别:
Harnessing monoclonal Treg for the treatment of autoimmune uveitis
利用单克隆 Treg 治疗自身免疫性葡萄膜炎
  • 批准号:
    9045643
  • 财政年份:
    2015
  • 资助金额:
    $ 41.1万
  • 项目类别:
Harnessing monoclonal Treg for the treatment of autoimmune uveitis
利用单克隆 Treg 治疗自身免疫性葡萄膜炎
  • 批准号:
    9265471
  • 财政年份:
    2015
  • 资助金额:
    $ 41.1万
  • 项目类别:

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