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
- 来源:
- 关键词:3-DimensionalAdenovirusesAdultAffectAmericanAnimal ModelAntigensArchivesArthralgiaArthritisAwardBiologyCD8B1 geneCellsCellular biologyCharacteristicsChemicalsChildChronicChronic Childhood ArthritisClinicalCoupledCytometryDataDevelopmentDimensionsDiseaseDrug EruptionsFlareFlow CytometryFluorescenceFoundationsFresh TissueFunctional disorderFundingHumanImageImmuneImmunityImmunofluorescence ImmunologicIndividualInflammationInflammatoryInflammatory ArthritisInterruptionIntra-Articular InjectionsInvestigationJointsLifeLongterm Follow-upLoxP-flanked alleleMediatingMediatorMemoryMetabolismModificationMusNational Institute of Arthritis, and Musculoskeletal, and Skin DiseasesPatientsPatternPhenotypePopulationPositioning AttributePsoriasisRecurrenceRecurrent diseaseReporterResearchResourcesRheumatoid ArthritisRheumatologyRoleSELL geneSiteSkinStressSurfaceSynovial MembraneSystemT memory cellT-LymphocyteTestingTherapeuticTimeTissuesanakinraarthritis therapycandidate identificationdesigndisabilitydisorder controlexperimental studyin vivoindividual patientinhibitorirradiationjoint inflammationjoint injurymigrationmouse modelnovelnovel strategiesresponsesingle-cell RNA sequencingskin disorderspectrographtissue resident memory T celltranscriptome
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)
专著数量(0)
科研奖励数量(0)
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
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:
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:
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