T resident memory cells in arthritis

关节炎中的T常驻记忆细胞

基本信息

  • 批准号:
    10684862
  • 负责人:
  • 金额:
    $ 42.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-01 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Inflammatory arthritis in adults and children is often characterized by periods of quiescent activity followed by disease flares. In any individual patient, the same joints typically flare repeatedly, in a pattern that usually establishes itself early in disease and then persists for years or decades. The hypothesis of this proposal is that this “joint-specific memory” reflects the presence of T resident memory (TRM) cells, whose targeting represents a new approach to arthritis therapy. TRM are a recently-described subset of long-lived T cells, either CD8 and CD4, that develop in skin and other tissues as a response to tissue inflammation, persisting for years thereafter to provide long-lasting site-specific immunity. TRM have never been described in joints. We have now developed compelling evidence for the presence of these cells in human arthritic synovium using three orthogonal approaches: single-cell RNAseq, a novel 3-dimensional synovial culture system, coupled with cytometry by time of flight (CyTOF), and Mantra multidimensional immunofluorescence imaging. Further, we have developed or adapted three animal models to develop new murine systems optimized for the study of recurrent, joint-specific, T cell-dependent inflammatory arthritis. Building upon these preliminary data, we propose two specific aims. First, we will perform a comprehensive characterization of human synovial TRM with respect to surface phenotype, mediators, transcriptome, and metabolism to compare synovial TRM with synovial effector memory T cells and “gold standard” TRM from human skin. Second, we will use our animal models to characterize the development and persistence of TRM over time; to test the possibility that these cells can re-activate arthritis upon antigen-independent triggering as well as antigen exposure; and employ local depletion to test TRM targeting as a novel approach to durable joint-specific arthritis therapy.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Peter A Nigrovic其他文献

Development of consensus best treatment plans for new-onset systemic juvenile idiopathic arthritis
  • DOI:
    10.1186/1546-0096-10-s1-a50
  • 发表时间:
    2012-07-13
  • 期刊:
  • 影响因子:
    2.300
  • 作者:
    Esi M Morgan DeWitt;Timothy Beukelman;Peter A Nigrovic;Karen Onel;Sampath Prahalad;Rayfel Schneider;Matthew Stoll;Carol A Wallace;Yukiko Kimura
  • 通讯作者:
    Yukiko Kimura
Disease characteristics and medication use in a multicenter cohort of children with juvenile idiopathic arthritis (JIA): preliminary analyses from the CARRAnet registry
  • DOI:
    10.1186/1546-0096-10-s1-a46
  • 发表时间:
    2012-07-13
  • 期刊:
  • 影响因子:
    2.300
  • 作者:
    Sarah Ringold;Timothy Beukelman;Esi M Morgan DeWitt;Marc Natter;Peter A Nigrovic;Yukiko Kimura
  • 通讯作者:
    Yukiko Kimura
Juvenile idiopathic arthritis is associated with potentially pathogenic glycosylation of IgG
  • DOI:
    10.1186/1546-0096-10-s1-a5
  • 发表时间:
    2012-07-13
  • 期刊:
  • 影响因子:
    2.300
  • 作者:
    Altan Ercan;Melissa Hazen;Mary Beth Son;Susan Kim;Fatma Dedeoglu;Robert P Sundel;Robert C Fuhlbrigge;Jing Cui;Nancy A Shadick;Michael E Weinblatt;Michael Spigarelli;David N Glass;Susan D Thompson;Peter A Nigrovic
  • 通讯作者:
    Peter A Nigrovic

Peter A Nigrovic的其他文献

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{{ truncateString('Peter A Nigrovic', 18)}}的其他基金

Impact of emperipolesis on platelet function
伸入对血小板功能的影响
  • 批准号:
    10705905
  • 财政年份:
    2022
  • 资助金额:
    $ 42.66万
  • 项目类别:
Modulation of neutrophil function through emperipolesis
通过伸入调节中性粒细胞功能
  • 批准号:
    10091401
  • 财政年份:
    2020
  • 资助金额:
    $ 42.66万
  • 项目类别:
Modulation of neutrophil function through emperipolesis
通过伸入调节中性粒细胞功能
  • 批准号:
    10656013
  • 财政年份:
    2020
  • 资助金额:
    $ 42.66万
  • 项目类别:
T resident memory cells in arthritis
关节炎中的 T 常驻记忆细胞
  • 批准号:
    10179324
  • 财政年份:
    2019
  • 资助金额:
    $ 42.66万
  • 项目类别:
T resident memory cells in arthritis
关节炎中的 T 常驻记忆细胞
  • 批准号:
    10609770
  • 财政年份:
    2019
  • 资助金额:
    $ 42.66万
  • 项目类别:
Bridging the gap between GWAS and mechanism in JIA
弥合 GWAS 和 JIA 机制之间的差距
  • 批准号:
    10064581
  • 财政年份:
    2018
  • 资助金额:
    $ 42.66万
  • 项目类别:
Bridging the gap between GWAS and mechanism in JIA
弥合 GWAS 和 JIA 机制之间的差距
  • 批准号:
    10675585
  • 财政年份:
    2018
  • 资助金额:
    $ 42.66万
  • 项目类别:
Bridging the gap between GWAS and mechanism in JIA
弥合 GWAS 和 JIA 机制之间的差距
  • 批准号:
    10622118
  • 财政年份:
    2018
  • 资助金额:
    $ 42.66万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10454987
  • 财政年份:
    2016
  • 资助金额:
    $ 42.66万
  • 项目类别:
Joint Biology Consortium Resource-based Center
联合生物学联盟资源中心
  • 批准号:
    10684880
  • 财政年份:
    2016
  • 资助金额:
    $ 42.66万
  • 项目类别:

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