Regulation of T helper cell functions by aryl hydrocarbon receptor

芳烃受体对 T 辅助细胞功能的调节

基本信息

  • 批准号:
    10596640
  • 负责人:
  • 金额:
    $ 37.5万
  • 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:
    2021-05-18 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract: Autoimmune diseases collectively affect over 23 million Americans and impose a huge burden of disease. Many autoimmune diseases are characterized by pathologic T cell-B cell interactions and production of autoantibodies. The T cell populations that help B cells in autoimmune diseases vary in phenotype and include T follicular helper (Tfh) cells, which reside in follicles of secondary lymphoid organs, as well as T peripheral helper (Tph) cells, which are B cell-helper T cells that migrate to inflamed peripheral tissues such as the rheumatoid joint. Tph cells and Tfh cells share the ability to recruit B cells via production of a B cell chemoattractant CXCL13 and then promote B cell differentiation through both surface interactions and secreted cytokines. The signals that regulate development and function of Tph cells and Tfh cells in autoimmunity remain incompletely described, and particularly little is known about T cell production of CXCL13. Our preliminary data reveal the aryl hydrocarbon receptor (AHR), a ligand-gated transcription factor, as a potent negative regulator of Tph and Tfh cell phenotype, with a dramatic effect on suppressing T cell CXCL13 production. In this project, we utilize human primary T cells and patient samples to evaluate the broad effects of AHR on Tph and Tfh cell development, function, and transcriptomic and epigenetic regulation. We will evaluate the direct targets of AHR in human T cells via ChIP-seq and seek to identify new transcriptional mediators downstream of AHR using CRISPR arrays. In addition, we will study synovial fluid and serum samples from patients with rheumatoid arthritis and comparator conditions to evaluate alterations in the extent of AHR agonist and antagonist activity in rheumatoid arthritis, a disease characterized by abundant accumulation of Tph cells in the target tissue. We expect that this project will reveal novel mechanisms mediated by AHR that regulate production of CXCL13 and key features of Tfh and Tph cell phenotypes. Understanding the molecular control of these key T cell functions may highlight new strategies to interfere with Tph and Tfh cells therapeutically.
项目总结/文摘:

项目成果

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Deepak Angara Rao其他文献

Deepak Angara Rao的其他文献

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{{ truncateString('Deepak Angara Rao', 18)}}的其他基金

Regulation of T helper cell functions by aryl hydrocarbon receptor
芳烃受体对 T 辅助细胞功能的调节
  • 批准号:
    10179018
  • 财政年份:
    2021
  • 资助金额:
    $ 37.5万
  • 项目类别:
Post-transcriptional Regulation of IL-21 in Human T Cells
人类 T 细胞中 IL-21 的转录后调控
  • 批准号:
    10404915
  • 财政年份:
    2021
  • 资助金额:
    $ 37.5万
  • 项目类别:
Regulation of T helper cell functions by aryl hydrocarbon receptor
芳烃受体对 T 辅助细胞功能的调节
  • 批准号:
    10407049
  • 财政年份:
    2021
  • 资助金额:
    $ 37.5万
  • 项目类别:
Molecular control of CD4 T cell ability to help B cells
CD4 T 细胞帮助 B 细胞能力的分子控制
  • 批准号:
    10357910
  • 财政年份:
    2018
  • 资助金额:
    $ 37.5万
  • 项目类别:

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