Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
基本信息
- 批准号:9247243
- 负责人:
- 金额:$ 39.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-01 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptive TransferAlveolar MacrophagesAntibodiesBindingC Type Lectin ReceptorsCell LineChimeric ProteinsChronic BronchitisChronic Obstructive Airway DiseaseCoculture TechniquesDataDevelopmentDiseaseDisease ProgressionEconomic BurdenEpithelial CellsExhibitsGoalsGranulocyte-Macrophage Colony-Stimulating FactorHealthImmunoprecipitationInflammationInjuryInvestigationKnockout MiceLaboratoriesLeadLeukocytesLigandsLungMacrophage ActivationMass Spectrum AnalysisMediatingModelingMolecularMorbidity - disease rateMouse StrainsMusNK Cell ActivationOxidative StressPathologyPathway interactionsPatientsPhenotypePlayProductionPublic HealthPulmonary EmphysemaPulmonary InflammationPulmonary PathologyQuality of lifeReceptor ActivationReceptor SignalingRegulationReporterResearchRoleSignal PathwaySignal TransductionSmokerStressSurfaceSystemTestingTherapeutic InterventionTissuesUp-Regulationairway inflammationbasechemokine receptorcigarette smoke-inducedcigarette smokingcytokineeffective therapyenvironmental tobacco smoke exposuremacrophagemigrationmonocytemortalityneutrophilnovelnovel therapeuticspersistent symptompublic health relevancereceptorresponsetargeted treatment
项目摘要
DESCRIPTION (provided by applicant): The health effects and economic burden associated with cigarette smoke (CS) exposure are overwhelming. The primary health effects are associated with symptoms of Chronic Obstructive Pulmonary Disease (COPD) including chronic bronchitis and emphysema. Currently, there are no effective therapies to deter disease progression in COPD patients. Over the last several decades, research has primarily focused on pathologies attributed to oxidative stress and the proteolytic imbalance associated with macrophage and neutrophil functions. Although the significance of these leukocytes and their effector functions are well documented, the mechanisms that lead to their aberrant activation by CS are poorly understood. The goal of our laboratory is to investigate the pathways whereby CS exposure activates pulmonary leukocytes. In this project, we present compelling evidence for a role of the CLEC5A activating receptor in macrophage activation in COPD. Our preliminary studies reveal that CLEC5A, expressed on alveolar macrophage, plays an integral role in macrophage activation following CS exposure. We generated a Clec5a-deficient mouse strain that reveals an essential role for CLEC5A in macrophage activation and pulmonary injury following CS exposure. The Clec5a-deficient mice fail to develop the hallmark features of COPD including pulmonary inflammation, macrophage accumulation and airspace enlargement. Furthermore, using a novel CLEC5A receptor fusion protein and CLEC5A-expressing reporter cell line, we provide evidence that a unique, previously undiscovered ligand for CLEC5A is expressed on CS-exposed pulmonary epithelial cells. These findings suggest a novel mechanism that promotes airway inflammation and pathologies in response to CS exposure.
描述(由申请人提供):与香烟烟雾(CS)暴露相关的健康影响和经济负担是压倒性的。主要健康影响与慢性阻塞性肺病(COPD)的症状有关,包括慢性支气管炎和肺气肿。目前,没有有效的治疗方法来阻止COPD患者的疾病进展。在过去的几十年里,研究主要集中在归因于氧化应激和与巨噬细胞和中性粒细胞功能相关的蛋白水解失衡的病理学上。虽然这些白细胞的意义和它们的效应器功能是有据可查的,但导致它们被CS异常激活的机制却知之甚少。我们实验室的目标是研究CS暴露激活肺白细胞的途径。在这个项目中,我们提出了令人信服的证据CLEC5A活化受体在COPD巨噬细胞活化中的作用。我们的初步研究表明,CLEC5A,肺泡巨噬细胞上表达,在巨噬细胞活化CS暴露后起着不可或缺的作用。我们产生了Clec5a缺陷型小鼠品系,其揭示了CLEC5A在CS暴露后的巨噬细胞活化和肺损伤中的重要作用。Clec5a缺陷小鼠未能发展出COPD的标志性特征,包括肺部炎症、巨噬细胞积聚和空域扩大。此外,使用一种新的CLEC5A受体融合蛋白和CLEC5A表达报告细胞系,我们提供的证据表明,一个独特的,以前未发现的CLEC5A配体表达CS暴露的肺上皮细胞。这些发现表明一种新的机制,促进气道炎症和病理反应的CS曝光。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michael Borchers其他文献
Michael Borchers的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michael Borchers', 18)}}的其他基金
Molecular and Cellular Pathogenesis of Pulmonary Langerhans Cell Histiocytosis
肺朗格汉斯细胞组织细胞增多症的分子和细胞发病机制
- 批准号:
10658208 - 财政年份:2023
- 资助金额:
$ 39.5万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10316151 - 财政年份:2020
- 资助金额:
$ 39.5万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10578653 - 财政年份:2020
- 资助金额:
$ 39.5万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10012049 - 财政年份:2020
- 资助金额:
$ 39.5万 - 项目类别:
Natural Killer Cell Functions in Lymphangioleiomyomatosis
自然杀伤细胞在淋巴管平滑肌瘤病中的功能
- 批准号:
10323021 - 财政年份:2019
- 资助金额:
$ 39.5万 - 项目类别:
Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
- 批准号:
8696486 - 财政年份:2014
- 资助金额:
$ 39.5万 - 项目类别:
Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
- 批准号:
9040253 - 财政年份:2014
- 资助金额:
$ 39.5万 - 项目类别:
Novel Reagents in Mouse Models of Autoimmune COPD
自身免疫性慢性阻塞性肺病小鼠模型中的新型试剂
- 批准号:
8166497 - 财政年份:2011
- 资助金额:
$ 39.5万 - 项目类别:
Novel Reagents in Mouse Models of Autoimmune COPD
自身免疫性慢性阻塞性肺病小鼠模型中的新型试剂
- 批准号:
8313878 - 财政年份:2011
- 资助金额:
$ 39.5万 - 项目类别:
Shared Mechanisms of Pulmonary Lymphocyte Activation by Bacteria and Toxicants
细菌和毒物激活肺淋巴细胞的共同机制
- 批准号:
7163144 - 财政年份:2006
- 资助金额:
$ 39.5万 - 项目类别:
相似海外基金
Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM
ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
- 批准号:
10682121 - 财政年份:2023
- 资助金额:
$ 39.5万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10576370 - 财政年份:2022
- 资助金额:
$ 39.5万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10387023 - 财政年份:2022
- 资助金额:
$ 39.5万 - 项目类别:
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10248409 - 财政年份:2019
- 资助金额:
$ 39.5万 - 项目类别:
A phase I clinical study of adoptive transfer of regulatory T cells (Tregs) and low-dose interleukin-2 (IL-2) for the treatment of chronic graft-versus-host disease (GVHD): gene-marking to inform rational combination therapy
调节性 T 细胞 (Treg) 和低剂量白细胞介素 2 (IL-2) 过继转移治疗慢性移植物抗宿主病 (GVHD) 的 I 期临床研究:基因标记为合理的联合治疗提供信息
- 批准号:
nhmrc : GNT1163111 - 财政年份:2019
- 资助金额:
$ 39.5万 - 项目类别:
Project Grants
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10462684 - 财政年份:2019
- 资助金额:
$ 39.5万 - 项目类别:
Gene edited lymphoid progenitors for adoptive transfer as a treatment of primary immunodeficiency
基因编辑的淋巴祖细胞用于过继转移作为原发性免疫缺陷的治疗
- 批准号:
398018062 - 财政年份:2018
- 资助金额:
$ 39.5万 - 项目类别:
Research Grants
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9308643 - 财政年份:2017
- 资助金额:
$ 39.5万 - 项目类别:
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9447149 - 财政年份:2017
- 资助金额:
$ 39.5万 - 项目类别:
Targeting Cancer miRNAs by Adoptive Transfer of Programmed B Lymphocytes
通过程序化 B 淋巴细胞的过继转移靶向癌症 miRNA
- 批准号:
8893915 - 财政年份:2014
- 资助金额:
$ 39.5万 - 项目类别: