Project 1: Regulation of CD9+ Monocyte & Macrophage Immune Functions in Atherosclerosis
项目1:CD9单核细胞的调控
基本信息
- 批准号:10334094
- 负责人:
- 金额:$ 4.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2022-06-02
- 项目状态:已结题
- 来源:
- 关键词:AngiographyAnti-Inflammatory AgentsAntigensAortaArterial Fatty StreakAtherosclerosisAutomobile DrivingB-LymphocytesBackBiological MarkersBloodBlood VesselsBody WeightBody mass indexCD14 geneCD36 geneCardiovascular DiseasesCause of DeathCell CommunicationCell membraneCell physiologyCellsCharacteristicsClinicalComplement ActivationCoronaryCytometryDevelopmentDisease ProgressionDisease modelFCGR3B geneFrequenciesFundingGene Expression ProfileGlycosylated hemoglobin AHomeostasisHumanHybridsIL1B geneImmuneImmunologic ReceptorsIndividualInflammationInflammatoryKnowledgeLeadLeukocytesLinkLipidsLocationLongitudinal StudiesMembraneMembrane LipidsMembrane ProteinsMetabolicMetabolismMulti-Ethnic Study of AtherosclerosisMusMyelogenousMyeloid CellsMyocardial InfarctionPathway AnalysisPathway interactionsPhenotypePlayPopulationProcessQuantitative Trait LociRegulationRoleSeverity of illnessShapesT-Cell ActivationT-LymphocyteTLR4 geneTNF geneTestingVirginiaVirusX-Ray Computed Tomographychemokinecohortcytokinegene inductionhigh dimensionalityhuman subjectimmune functionimmunomodulatory therapiesimmunoregulationlipid metabolismmacrophagemigrationmonocytemouse modeloxidized low density lipoproteinprogramsprotein biomarkersreceptorscavenger receptorsextraffickingtranscriptome sequencingtranscriptomicstumoruptake
项目摘要
Project 1 Summary
In the last cycle of this PPG, we identified eight subsets of human monocytes in healthy individuals using
high dimensional mass cytometry. These subsets have now been confirmed in other studies. We
discovered that some monocyte subsets expressed the tetraspanin CD9, and that these CD9+ monocyte
subsets positively correlated with cardiovascular disease (CAD) severity in humans. The tetraspanin
CD9 facilitates the organization and clustering of receptors within membranes. CD9 regulates MHCII
trafficking in myeloid cells, which is critical for T cell activation, and aids in macrophage uptake of oxLDL
by organizing plasma membrane clustering of the scavenger receptor CD36. Thus, CD9 location in
membranes allows for the modulation of immune receptor activity. Functional pathway analysis of
CD9+ monocytes revealed induction of genes involved in inflammation, leukocyte migration, and
complement activation pathways. Although such characteristics would be important for the homeostatic
functions of monocytes in clearing viruses, tumors, and damaged host cells, we surmise that these
functions could instead become deleterious in the vessel wall, and promote atherosclerosis. We also
have recent evidence to suggest that CD9+ monocytes give rise to CD9+ macrophages in the aortic wall.
Here, we hypothesize that immunomodulatory CD9+ monocytes and CD9+ macrophages promote
atherosclerosis progression by driving a pro-inflammatory cytokine program, regulating plaque
macrophage lipid content, and interacting with T cells and B cells to drive plaque progression.
We will test this hypothesis in two specific aims, where we study both humans with CAD and mouse
models of atherosclerosis. Aim 1 will functionally study CD9+ monocyte subsets in human subjects from
well-characterized clinical cohorts, who have clinically-documented low and high CAD, and in subjects
who are participating in a longitudinal study of plaque progression. Aim 2 will mechanistically study the
functions and metabolism of CD9+ macrophage subsets, and will directly test the role of monocyte and
macrophage CD9 expression in regulating atherosclerosis progression. We will utilize unique monocyte-
specific mouse models (mice lacking nonclassical monocytes (E2)) and mice lacking classical monocytes
(Ccr2-/-) to functionally examine how CD9 in either classical or nonclassical monocytes modulates
atherosclerosis development. Together, these completed aims in this renewal could lead to new
biomarkers and therapies for immunomodulation of monocytes in atherosclerosis.
项目1概述
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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Catherine C Hedrick其他文献
Stressing out stem cells: linking stress and hematopoiesis in cardiovascular disease
应激干细胞:将心血管疾病中的应激与造血作用联系起来
- DOI:
10.1038/nm.3631 - 发表时间:
2014-07-07 - 期刊:
- 影响因子:50.000
- 作者:
Richard N Hanna;Catherine C Hedrick - 通讯作者:
Catherine C Hedrick
Catherine C Hedrick的其他文献
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{{ truncateString('Catherine C Hedrick', 18)}}的其他基金
Neutrophil Development During Inflammation and Atherosclerosis
炎症和动脉粥样硬化期间中性粒细胞的发育
- 批准号:
10651786 - 财政年份:2021
- 资助金额:
$ 4.33万 - 项目类别:
Neutrophil Development During Inflammation and Atherosclerosis
炎症和动脉粥样硬化期间中性粒细胞的发育
- 批准号:
10270897 - 财政年份:2021
- 资助金额:
$ 4.33万 - 项目类别:
Neutrophil Development During Inflammation and Atherosclerosis
炎症和动脉粥样硬化期间中性粒细胞的发育
- 批准号:
10470240 - 财政年份:2021
- 资助金额:
$ 4.33万 - 项目类别:
2019 Atherosclerosis Gordon Research Conference and Gordon Research Seminar
2019年动脉粥样硬化戈登研究大会暨戈登研究研讨会
- 批准号:
9759445 - 财政年份:2019
- 资助金额:
$ 4.33万 - 项目类别:
Protective Role of Nonclassical Monocytes in Immunotherapies for Solid Cancers
非经典单核细胞在实体癌免疫治疗中的保护作用
- 批准号:
9899213 - 财政年份:2018
- 资助金额:
$ 4.33万 - 项目类别:
Protective Role of Nonclassical Monocytes in Immunotherapies for Solid Cancers
非经典单核细胞在实体癌免疫治疗中的保护作用
- 批准号:
9471276 - 财政年份:2018
- 资助金额:
$ 4.33万 - 项目类别:
Monocyte Subsets & Immunity in Mouse and Human Atherosclerosis
单核细胞亚群
- 批准号:
10188605 - 财政年份:2017
- 资助金额:
$ 4.33万 - 项目类别:
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