TIM-1, TIM-3 and TIM-4: A gene family that regulates tolerance and immunity
TIM-1、TIM-3 和 TIM-4:调节耐受性和免疫性的基因家族
基本信息
- 批准号:7995554
- 负责人:
- 金额:$ 20.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-09-30 至 2015-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAllergensAntigensApoptoticAsthmaAtopic DermatitisBreedingCell CommunicationCellsCongenic MiceDendritic CellsDevelopmentDiseaseDisease susceptibilityExposure toFoodFood HypersensitivityGene FamilyGeneral PopulationGenerationsGenesGenetic PolymorphismGenetic VariationGoalsGrantGut associated lymphoid tissueHomeostasisHypersensitivityImmuneImmune responseImmunityInbred BALB C MiceInflammatoryInstructionLaboratoriesLamina PropriaLeadLinkMediatingMesenteryMolecularMusPathway interactionsPhosphatidylserinesPlayProteinsPublic HealthReagentRegulationRegulatory T-LymphocyteRelative (related person)Rheumatoid ArthritisRoleSignal TransductionSusceptibility GeneT cell responseT-Cell ActivationT-LymphocyteT-Lymphocyte SubsetsTh1 CellsTh1/Th2 Differentiation PathwayTh2 CellsTissuesTransgenic MiceVariantairway hyperresponsivenessallergic responseatopycell typecongenicexperienceimprovedin vivolymph nodesmouse modelnoveloral toleranceperipheral tolerancephosphatidylserine receptorpreventreceptorresponseuptake
项目摘要
PROJECT SUMMARY (See instructions):
The TIM gene family was identified using a congenic mouse model in which polymorphisms in TIM-1
and TIM-3 wre associated with Th1-Th2 differentiation and allergen-induced ainway hyperreactivity (AHR) between BALB/c and congenic HBA mice. The long-term goals of Project 3 are to understand how the Tim genes regulate peripheral tolerance, adaptive immune responses, and allergy. In the previous grant period we showed that TIM-1 is an important costimulatory molecule for T cells, that TIM-1 and TIM-4 modulate T cell responses and the development of tolerance, and that TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), a key molecule for recognition and uptake of apoptotic cells. We have found that TIM-3, expressed on Th1 cells and APC, is also a receptor for PtdSer and that the allelic variants of TIM-3 associated with asthma differ in their recognition of PtdSer. These results together suggest a new paradigm for TIM proteins as PtdSer receptors that by regulating the recognition and clearance of apoptotic cells, can regulate tissue homeostasis, T cell responses and the induction of peripheral tolerance.
In Specific Aim 1 we will determine the mechanisms by which TIM-4 expressed on APC, and TIM-1,
expressed on activated T cells and Th2 cells, regulate oral tolerance and prevent food allergy. We will
examine mechanisms by which TIM-4 blockade inhibits oral tolerance induction. In Specific Aim 2, we will characterize the cell types and APC subset(s) in the lamina propria and mesenteric lymph node that express TIM-4, the conditions that modulate expression of TIM-3 and TIM-4 following exposure to danger signals such as bacterial products that initiate food allergy. We will examine the consequences of T cell interaction with TIM-expressing APC on T cell subset differentiation. In Specific Aim 3 we will investigate the role of TIM-3 polymorphic variants, which we have recently shown differ in recognition of apoptotic cells, in modulation of immune responses in BALB/c and HBA mice, and determine the roles of TIM-1 and TIM-3 in modulating the development of airway hyperreactivity in these strains.
We have developed unique reagents that will enable us to accomplish these goals. We have
generated panels of anti-TIM-1 and TIM-4 mAbs, we have generated TIM-4 and TIM-1 transgenic mice, and TlM-1 deficient mice are now breeding in our colony. Our laboratory has extensive experience in the study of tolerance as a mechanism that protects against Th2-driven immune responses and in the study of dendritic cells (DCs) and antigen-specific CD4+ Tpeg cells. These studies will greatly improve our understanding of immune regulation and lead to new therapies for inflammatory diseases.
项目概述(见说明):
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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Rosemarie H DeKruyff其他文献
Rosemarie H DeKruyff的其他文献
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{{ truncateString('Rosemarie H DeKruyff', 18)}}的其他基金
TIM recognition of PtdSer on apoptotic cells and the regulation of immunity
TIM对凋亡细胞PtdSer的识别及免疫调节
- 批准号:
8495892 - 财政年份:2010
- 资助金额:
$ 20.59万 - 项目类别:
TIM recognition of PtdSer on apoptotic cells and the regulation of immunity
TIM对凋亡细胞PtdSer的识别及免疫调节
- 批准号:
8704253 - 财政年份:2010
- 资助金额:
$ 20.59万 - 项目类别:
TIM recognition of PtdSer on apoptotic cells and the regulation of immunity
TIM对凋亡细胞PtdSer的识别及免疫调节
- 批准号:
8082683 - 财政年份:2010
- 资助金额:
$ 20.59万 - 项目类别:
TIM recognition of PtdSer on apoptotic cells and the regulation of immunity
TIM对凋亡细胞PtdSer的识别及免疫调节
- 批准号:
7949426 - 财政年份:2010
- 资助金额:
$ 20.59万 - 项目类别:
TIM recognition of PtdSer on apoptotic cells and the regulation of immunity
TIM对凋亡细胞PtdSer的识别及免疫调节
- 批准号:
8288920 - 财政年份:2010
- 资助金额:
$ 20.59万 - 项目类别:
TIM-1, TIM-3 and TIM-4: A gene family that regulates tolerance and immunity
TIM-1、TIM-3 和 TIM-4:调节耐受性和免疫性的基因家族
- 批准号:
8306826 - 财政年份:2003
- 资助金额:
$ 20.59万 - 项目类别:
TIM-1, TIM-3 and TIM-4: A gene family that regulates tolerance and immunity
TIM-1、TIM-3 和 TIM-4:调节耐受性和免疫性的基因家族
- 批准号:
8831793 - 财政年份:2003
- 资助金额:
$ 20.59万 - 项目类别:
TIM-1, TIM-3 and TIM-4: A gene family that regulates tolerance and immunity
TIM-1、TIM-3 和 TIM-4:调节耐受性和免疫性的基因家族
- 批准号:
8380754 - 财政年份:2003
- 资助金额:
$ 20.59万 - 项目类别:
TIM-1, TIM-3 and TIM-4: A gene family that regulates tolerance and immunity
TIM-1、TIM-3 和 TIM-4:调节耐受性和免疫性的基因家族
- 批准号:
8507123 - 财政年份:2003
- 资助金额:
$ 20.59万 - 项目类别:
Differential Activation Requirements of CD4+ T Cells
CD4 T 细胞的差异激活要求
- 批准号:
6382727 - 财政年份:2001
- 资助金额:
$ 20.59万 - 项目类别:
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