Protective role of dectin-1 signaling in an animal model of Multiple Sclerosis
dectin-1 信号传导在多发性硬化症动物模型中的保护作用
基本信息
- 批准号:9756132
- 负责人:
- 金额:$ 3.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAffectAgonistAnimal ModelAutoimmune DiseasesAutoimmune Diseases of the Nervous SystemAutoimmunityBindingBone MarrowC Type Lectin ReceptorsCalcium SignalingCell WallCellsCentral Nervous System DiseasesChimera organismDataDevelopmentDiseaseExperimental Autoimmune EncephalomyelitisGoalsImmuneImmune System DiseasesImmune responseImmune signalingImmunotherapyIn VitroIncidenceInjectionsInnate Immune ResponseInnate Immune SystemKnock-outLigandsLinkMediatingMicrogliaMissionModelingMultiple SclerosisMusMycosesMyeloid CellsNational Institute of Allergy and Infectious DiseaseNerve RegenerationNervous System TraumaNeuraxisNuclearPathway interactionsPatientsPattern recognition receptorPeripheralPublic HealthRAF1 geneRadiation ToleranceResearchRoleSeveritiesSignal PathwaySignal TransductionSpinal cord damageTestingUp-RegulationWorkbasecell typedectin 1insightneuroinflammationneutrophilnoveloncostatin Mpreventpromoterprotective effectradioresistantreceptorrepairedtranscription factor
项目摘要
ABSTRACT
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) affecting an estimated
2.5 million people worldwide. Recent work strongly implicates the innate immune system in the development of
both MS and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). C-type Lectin Receptors
(CLR) are a major class of pattern recognition receptors (PRR) that can initiate innate immune responses, but
their role in autoimmune disease and in MS is largely unknown. My preliminary data demonstrates that the
CLR dectin-1 has an unexpected protective role in EAE. Mice lacking dectin-1 develop more severe EAE, and
a single injection of a dectin-1 agonist can reduce disease incidence and severity. The primary objective of this
project is to dissect the mechanisms by which dectin-1 signaling is protective in CNS autoimmune disease,
using EAE as a model. Recently, I found that dectin-1 signaling can upregulate the neuroprotective factor,
Oncostatin M (Osm) in myeloid cells. Based on my preliminary data, this upregulation appears to occur through
a non-canonical dectin-1 signaling pathway independent of CARD9 and RAF1. Additionally, I found that a
recently identified endogenous ligand for dectin-1 is upregulated in EAE and can similarly induce Osm. In this
proposal, I will determine the cell subsets and ligands responsible for protective dectin-1 signaling and I will
uncover the mechanism and function of dectin-1 induced Osm in EAE. By identifying and dissecting protective
innate immune signaling by dectin-1 in EAE, this research has the potential to reveal novel targets for
immunotherapy in MS.
摘要
多发性硬化症(MS)是中枢神经系统(CNS)的自身免疫性疾病,影响估计的
2.5全球百万人。最近的工作强烈暗示先天免疫系统在发展中,
MS及其动物模型实验性自身免疫性脑脊髓炎(EAE)。c型凝集素受体
(CLR)是一种主要类型的模式识别受体(PRR),可以启动先天免疫反应,但
它们在自身免疫性疾病和MS中的作用在很大程度上是未知的。我的初步数据表明,
EAE中的EADECTIN-1具有意想不到的保护作用。缺乏dectin-1的小鼠发生更严重的EAE,
单次注射dectin-1激动剂可以降低疾病的发病率和严重程度。这项工作的主要目的是
该项目旨在剖析dectin-1信号在CNS自身免疫性疾病中的保护机制,
使用EAE作为模型。最近,我发现dectin-1信号可以上调神经保护因子,
骨髓细胞中的制瘤素M(Osm)。根据我的初步数据,这种上调似乎发生在
一种不依赖于CARD 9和RAF 1的非经典dectin-1信号通路。此外,我发现,
最近鉴定的dectin-1的内源性配体在EAE中上调,并且可以类似地诱导Osm。在这
建议,我将确定负责保护dectin-1信号传导的细胞亚群和配体,
揭示dectin-1诱导Osm在EAE中的作用机制。通过识别和解剖
通过dectin-1在EAE中的先天免疫信号传导,这项研究有可能揭示新的靶点,
免疫疗法在MS
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Marion Elizabeth Deerhake其他文献
Marion Elizabeth Deerhake的其他文献
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{{ truncateString('Marion Elizabeth Deerhake', 18)}}的其他基金
Protective role of dectin-1 signaling in an animal model of Multiple Sclerosis
dectin-1 信号传导在多发性硬化症动物模型中的保护作用
- 批准号:
9974290 - 财政年份:2018
- 资助金额:
$ 3.68万 - 项目类别:
Protective role of dectin-1 signaling in an animal model of Multiple Sclerosis
dectin-1 信号传导在多发性硬化症动物模型中的保护作用
- 批准号:
10170219 - 财政年份:2018
- 资助金额:
$ 3.68万 - 项目类别:
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