Investigating monocyte dysfunction in Down Syndrome
研究唐氏综合症的单核细胞功能障碍
基本信息
- 批准号:10854106
- 负责人:
- 金额:$ 38.37万
- 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:2019-07-24 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdministrative SupplementAdultArthritisAutoimmune DiseasesB-LymphocytesBasic ScienceCD14 geneCellsCellular Indexing of Transcriptomes and Epitopes by SequencingChildChildhoodChronic Childhood ArthritisCollaborationsComplicationDataData SetDiseaseDown SyndromeFCGR3B geneFreezingFunctional disorderFundingFutureGoalsHashimoto DiseaseImmuneImmune System DiseasesImmune responseImmunityIncidenceIndividualInflammatoryInflammatory ArthritisInflammatory ResponseInnate Immune ResponseInnate Immune SystemInsulin-Dependent Diabetes MellitusInterferonsInterleukin-6KnowledgeLeadLearningLeukocytesLightLongevityMacrophageMacrophage ActivationMacrophage activation syndromeMediatingMedical centerNational Institute of Arthritis, and Musculoskeletal, and Skin DiseasesParentsParticipantPathogenesisPathogenicityPathologyPatientsPeripheral Blood Mononuclear CellPhenotypePhosphorylationPhysiciansPopulationReceptor SignalingRegistriesResearch InstituteRheumatismRheumatoid ArthritisRoleSTAT1 geneSamplingSeveritiesSystemSystemic Lupus ErythematosusT-LymphocyteTissuesToll-like receptorsVirginiaVirus DiseasesWorkadaptive immune responsebiobankcytokinedata sharingexperimental studyhigh rewardhigh riskhuman modelinsightmonocytemouse modelparent grantprogramsresponsesingle-cell RNA sequencingsystemic juvenile idiopathic arthritisvaccine response
项目摘要
PROJECT SUMMARY
We are requesting an Administrative Supplement for the INCLUDE Project for R01 AR076242 “IRF5 and
Macrophage Activation Syndrome in systemic Juvenile Idiopathic Arthritis”. The proposed studies for the in this
Supplement are within the scope of the active parent grant, focused on Down syndrome (DS) and are aligned
with the goals of the overall INCLUDE Project—Component 1: Targeted high risk – high reward basic science
studies highly relevant to DS. Our studies take advantage of a growing registry and biorepository of DS
individuals that has been established at the Benaroya Research Institute by Drs. Bernard Khor and Jane
Buckner. The objectives of this administrative supplement are to better understand innate immune alterations in
DS. Individuals with DS have immune dysfunction evidenced by decreased vaccine responses, increased
severity of viral infections and increased incidence of certain autoimmune diseases, including autoimmune
thyroiditis, type 1 diabetes and juvenile idiopathic arthritis (JIA). DS individuals also have increased type 1 IFN
responses and increased amounts of some inflammatory cytokines and specific alterations in T and B cells.
However, how these alterations lead to the overall changes in immunity in DS is not well-understood. Importantly,
there has been much focus on adaptive immune responses in DS, with less focus on cells of the innate immune
system, including monocytes and macrophages, important in the pathogenesis of many autoimmune diseases,
including (JIA).
This supplement is within the scope of the Parent R01 as it: 1) investigates monocytes and TLR
responses in these cells, which are the focus of the parent R01, 2) relates to a form of juvenile arthritis seen
more frequently in individuals with DS, as the parent grant focuses on another form of juvenile arthritis (systemic
juvenile idiopathic arthritis (SJIA)), and 3) will leverage our existing single cell RNA-Seq (scRNA-Seq) data
funded by the parent R01. Data generated from this supplement will inform our parent R01 by giving us additional
monocyte scRNA-Seq datasets to compare with our already generated scRNA-Seq datasets from children with
SJIA-associated MAS and matched controls. This supplement is within NIAMS INCLUDE Program priorities to
better understand arthritic disorders in DS across the lifepan. Because monocytes and macrophages are key
players in pathogenesis of all forms of arthritis, understanding whether these cells and their responses are
dysregulated in DS will lead to a better understanding of their contributions to the increased incidence of arthritis
in children with DS.
项目总结
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Detection of neutrophil extracellular traps in patient plasma: method development and validation in systemic lupus erythematosus and healthy donors that carry IRF5 genetic risk.
- DOI:10.3389/fimmu.2022.951254
- 发表时间:2022
- 期刊:
- 影响因子:7.3
- 作者:Matta, Bharati;Battaglia, Jenna;Barnes, Betsy J.
- 通讯作者:Barnes, Betsy J.
Aim2 Couples With Ube2i for Sumoylation-Mediated Repression of Interferon Signatures in Systemic Lupus Erythematosus.
- DOI:10.1002/art.41677
- 发表时间:2021-08
- 期刊:
- 影响因子:0
- 作者:Lu A;Wu S;Niu J;Cui M;Chen M;Clapp WL;Barnes BJ;Meng G
- 通讯作者:Meng G
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Betsy J Barnes其他文献
Betsy J Barnes的其他文献
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{{ truncateString('Betsy J Barnes', 18)}}的其他基金
Implications for Speckled proteins 110 and 140 in adaptive immunity
斑点蛋白 110 和 140 对适应性免疫的影响
- 批准号:
10726020 - 财政年份:2023
- 资助金额:
$ 38.37万 - 项目类别:
New role(s) for IRF5 as a regulator of tau accumulation in Alzheimer’s disease
IRF5 在阿尔茨海默病中调节 tau 蛋白积累的新作用
- 批准号:
10302599 - 财政年份:2021
- 资助金额:
$ 38.37万 - 项目类别:
IRF5 and Macrophage Activation Syndrome in systemic Juvenile Idiopathic Arthritis
系统性幼年特发性关节炎中的 IRF5 和巨噬细胞激活综合征
- 批准号:
10199939 - 财政年份:2019
- 资助金额:
$ 38.37万 - 项目类别:
IRF5 and Macrophage Activation Syndrome in systemic Juvenile Idiopathic Arthritis
系统性幼年特发性关节炎中的 IRF5 和巨噬细胞激活综合征
- 批准号:
10454915 - 财政年份:2019
- 资助金额:
$ 38.37万 - 项目类别:
IRF5 and Macrophage Activation Syndrome in systemic Juvenile Idiopathic Arthritis
系统性幼年特发性关节炎中的 IRF5 和巨噬细胞激活综合征
- 批准号:
9982787 - 财政年份:2019
- 资助金额:
$ 38.37万 - 项目类别:
IRF5 and Macrophage Activation Syndrome in systemic Juvenile Idiopathic Arthritis
系统性幼年特发性关节炎中的 IRF5 和巨噬细胞激活综合征
- 批准号:
10663266 - 财政年份:2019
- 资助金额:
$ 38.37万 - 项目类别:
Determining the function of IRF5 tumor suppressor in HCV pathogenesis
确定 IRF5 抑癌基因在 HCV 发病机制中的功能
- 批准号:
9108325 - 财政年份:2015
- 资助金额:
$ 38.37万 - 项目类别:
Determining the function of IRF5 tumor suppressor in HCV pathogenesis
确定 IRF5 抑癌基因在 HCV 发病机制中的功能
- 批准号:
9147052 - 财政年份:2015
- 资助金额:
$ 38.37万 - 项目类别:
IRF5-TNPO3 locus: Inclusion of TNPO3 as a unique regulator of IRF5 expression an
IRF5-TNPO3 基因座:将 TNPO3 作为 IRF5 表达的独特调节因子纳入其中
- 批准号:
8664081 - 财政年份:2014
- 资助金额:
$ 38.37万 - 项目类别:
IRF5-TNPO3 locus: Inclusion of TNPO3 as a unique regulator of IRF5 expression an
IRF5-TNPO3 基因座:将 TNPO3 作为 IRF5 表达的独特调节因子纳入其中
- 批准号:
9220283 - 财政年份:2014
- 资助金额:
$ 38.37万 - 项目类别:
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