Mechanisms by which CD74 Contributes to Traumatic Brain Injury
CD74 导致创伤性脑损伤的机制
基本信息
- 批准号:10241518
- 负责人:
- 金额:$ 39.91万
- 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:2019-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelAnimalsAnti-Inflammatory AgentsAntigen PresentationAntigensAstrocytesAttentionAutoimmunityBehavioralBindingBortezomibBrainBrefeldin ACathepsinsCell surfaceCellsChronicChronic HeadachesCleaved cellClinicalCystatinsDataEmotionalEpilepsyGoalsHumanImmuneImmune responseImmune systemImpaired cognitionInflammationInflammatory ResponseInnate Immune ResponseLearningLengthLysosomesMediatingMemoryMigration Inhibitory FactorModelingMolecularMusNerve DegenerationNervous System TraumaNeurologicNeurologic DysfunctionsOutcomePathogenesisPatientsPeptidesPersonsPlayProteinsReportingRoleSUI1 geneSignal TransductionSpleenSuggestionSyndromeT-LymphocyteTherapeuticTimeTraumatic Brain Injuryadaptive immune responseadaptive immunityantigen bindingbasebehavioral outcomedisabilityeffective therapyexperimental studyfluid percussion injuryimprovedimproved outcomeinhibitor/antagonistneurobehavioralneuroinflammationneuropathologynew therapeutic targetnovelnovel therapeuticsoptimal treatmentspreventprotein functionresponsetreatment strategy
项目摘要
Project Summary/ Abstract
Traumatic brain injury (TBI), and the ensuing post-traumatic behavioral and
neurological syndromes, are serious clinical problems. Approximately 5 million
people in the U.S. are living with the chronic consequences of TBI, and optimal
treatment strategies are lacking. We have discovered that specific components of
the immune system contribute to neuropathology after a TBI. More specifically,
we have discovered that CD74, a protein that functions via unique mechanisms
that distinctly contribute to either the innate or the adaptive immune response, can
be manipulated to improve neurodegeneration and behavioral outcomes after TBI.
Our proposal is based on three primary observations:
1) Our preliminary data implicating full-length CD74 signaling via macrophage
migration inhibitory factor (MIF)-binding in the astrocytic response to TBI; 2) Our
data indicating that depleting full-length CD74 or antagonizing the proteolytic
cleavage product(s) of CD74, class II invariant peptide (CLIP), are anti-
inflammatory and neuroprotective after TBI; 3) Recent evidence from human
clinical TBI patients and experimental TBI in animal models, showing strong
evidence for an adaptive immune response, potentially including autoimmunity.
Taken together, these studies are important because: A) they will assess the
distinct contributions of CD74 to the innate and adaptive immune responses
following TBI; B) they will distinguish between the unique mechanisms of CD74
that contribute to TBI-induced neuropathology and post-traumatic behavioral
syndromes; and C) they will determine if targeting specific components of CD74
might be a potential therapeutic strategy following TBI.
项目总结/摘要
创伤性脑损伤(TBI),以及随后的创伤后行为和
神经综合征是严重的临床问题。约5百万
美国人生活在TBI的慢性后果中,
缺乏治疗策略。我们发现,
免疫系统对创伤性脑损伤后的神经病理学有贡献。更具体地说,
我们发现CD 74,一种通过独特机制发挥作用的蛋白质,
明显有助于先天性或适应性免疫反应,
被操纵以改善TBI后的神经变性和行为结果。
我们的建议基于三个主要观察:
1)我们的初步数据表明全长CD 74信号通过巨噬细胞
星形胶质细胞对TBI的反应中的迁移抑制因子(MIF)结合; 2)我们的
数据表明,消耗全长CD 74或拮抗蛋白水解作用,
CD 74的切割产物,II类不变肽(CLIP),是抗-
TBI后的炎症和神经保护作用; 3)来自人类的最新证据
临床TBI患者和实验TBI动物模型中,显示出强烈的
适应性免疫反应的证据,可能包括自身免疫。
总的来说,这些研究很重要,因为:A)它们将评估
CD 74对先天性和适应性免疫应答的不同贡献
B)它们将区分CD 74的独特机制,
导致TBI诱导的神经病理学和创伤后行为
C)他们将确定是否靶向CD 74的特定组分,
可能是TBI后潜在的治疗策略。
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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M. Karen Newell Rogers其他文献
M. Karen Newell Rogers的其他文献
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{{ truncateString('M. Karen Newell Rogers', 18)}}的其他基金
Mechanisms by which CD74 Contributes to Traumatic Brain Injury
CD74 导致创伤性脑损伤的机制
- 批准号:
10493357 - 财政年份:2019
- 资助金额:
$ 39.91万 - 项目类别:
Mechanisms by which CD74 Contributes to Traumatic Brain Injury
CD74 导致创伤性脑损伤的机制
- 批准号:
10001758 - 财政年份:2019
- 资助金额:
$ 39.91万 - 项目类别:
Mechanisms by which CD74 Contributes to Traumatic Brain Injury
CD74 导致创伤性脑损伤的机制
- 批准号:
10024091 - 财政年份:2019
- 资助金额:
$ 39.91万 - 项目类别:
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