Control of CD8+ T cell migration and activation by Flightless-1
Flightless-1 控制 CD8 T 细胞迁移和激活
基本信息
- 批准号:10366045
- 负责人:
- 金额:$ 21.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-05 至 2023-02-28
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAntigen-Presenting CellsBundlingCCL21 geneCD28 geneCD8-Positive T-LymphocytesCDC42 geneCellsCellular ImmunityCellular StructuresComplexCytoplasmic GranulesCytoskeletonDataDevelopmentDistalDrosophila genusEmbryoEquilibriumExocytosisF-ActinFamilyFamily memberG ActinGelsolinGenesGrowthHomeostasisImmunologic SurveillanceImpairmentIntegrinsKnockout MiceLeucine-Rich RepeatLinkLymphoid TissueMature T-LymphocyteMediatingMicrofilamentsMolecularMonomeric GTP-Binding ProteinsMusMuscleMyofibrilsN-terminalPeripheralPhysiologicalPolymersPositioning AttributeProcessProtein FamilyProteinsRoleSignal PathwaySignal TransductionSiteStructureT cell responseT-Cell ActivationT-Cell ReceptorT-LymphocyteTechniquesTestingTissuesWASP proteinactin capping proteinbasecell motilitychemokineconditional knockoutcytotoxicimmunological synapseimmunological synapse formationin vivoinnovationinsightmembermigrationmouse modelnovelpolarized cellprotein protein interactionresponserho
项目摘要
PROJECT SUMMARY
Adaptive immune surveillance depends on the ability of T cells to successfully migrate through secondary
lymphoid tissues and form immune-synapses with antigen-presenting cells. Precise and dynamic organization
of the actin cytoskeleton is essential for both of these processes. In migrating T cells rapid reorganization of the
actin cytoskeleton is essential for cell polarization and chemotactic responses required for tissue entry and
proper micro-environmental positioning. During T cell activation, changes in the actin cytoskeleton control proper
formation of the immunological synapse, a highly organized cellular structure that allows T cells to properly
integrate signals from the T cell receptor with those from co-stimulatory molecules such as CD28 and integrins
such as LFA-1 (αLβ2). Flightless-1 (Flii) was initially identified in Drosophila as an actin modifying protein that
controls actin myofibril structure in the muscles that control flight. Flii contains an N-terminal leucine-rich repeat
(LRR) domain that facilitates protein-protein interaction and has been implicated in control of Ras activation of
Erk/Mapk signaling, Rac1 activation and PI3K signaling. The Flii C-terminus encodes 6 gelsolin-related domains
that can interact with actin and regulate actin filament assembly/disassembly. Based on its unique domain
structure, we hypothesize that Flii acts as a key regulator of CD8+ T cell homeostasis and function by linking
changes in the actin cytoskeleton during cell migration and activation with spatial control of various signaling
cascades. We will use state-of-the-art cellular and molecular techniques to study Flii function in physiologically
relevant and innovative mouse models. Completion of these studies will provide important new insights into a
novel and completely uncharacterized signaling hub that regulates CD8+ T cell-mediated immunity.
项目总结
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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Daniel J Campbell其他文献
133 CARDIAC PERFORMANCE, EXERCISE CAPACITY AND PULMONARY FUNCTION AFTER FONTAN SURGERY
Fontan 手术后心脏功能、运动能力和肺功能
- DOI:
10.1203/00006450-198504000-00163 - 发表时间:
1985-04-01 - 期刊:
- 影响因子:3.100
- 作者:
David G Ruschhaupt;Daniel J Campbell;Otto G Thilenius;Robert L Replogle;Rene A Arcilla - 通讯作者:
Rene A Arcilla
Evaluating YouTube Videos on Facelift Surgery for Facial Rejuvenation as a Resource for Patients
评估有关面部年轻化整容手术的 YouTube 视频作为患者的资源
- DOI:
10.1177/00034894231154410 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Zachary T Elliot;Joseph S Lu;Daniel J Campbell;Kevin B Xiao;Vanessa Christopher;Howard Krein;R. Heffelfinger - 通讯作者:
R. Heffelfinger
Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.
接受初次手术与放化疗治疗 T1-T2 口咽鳞状细胞癌的患者功能和生存结果的差异。
- DOI:
10.1001/jamaoto.2023.1944 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Dev R Amin;R. Philips;Dylan G Bertoni;Eric V Mastrolonardo;Daniel J Campbell;A. Agarwal;Sruti Tekumalla;Zachary D Urdang;A. Luginbuhl;D. Cognetti;Joseph M. Curry - 通讯作者:
Joseph M. Curry
Evaluating ChatGPT responses on thyroid nodules for patient education.
评估 ChatGPT 对甲状腺结节的反应以进行患者教育。
- DOI:
10.1089/thy.2023.0491 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Daniel J Campbell;Leonard E Estephan;Elliott Sina;Eric V Mastrolonardo;Rahul Alapati;Dev R Amin;Elizabeth Cottrill - 通讯作者:
Elizabeth Cottrill
Evaluating ChatGPT Responses on Atrial Fibrillation for Patient Education
评估 ChatGPT 对心房颤动的反应以进行患者教育
- DOI:
10.7759/cureus.61680 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Thomas J Lee;Daniel J Campbell;Abhinav K Rao;Afif Hossain;Omar Elkattawy;Navid Radfar;Paul Lee;Julius M Gardin - 通讯作者:
Julius M Gardin
Daniel J Campbell的其他文献
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{{ truncateString('Daniel J Campbell', 18)}}的其他基金
Reprogramming of tissue structural cells by cutaneous CD4+ T cells
皮肤 CD4 T 细胞对组织结构细胞的重编程
- 批准号:
10608777 - 财政年份:2023
- 资助金额:
$ 21.76万 - 项目类别:
Control of CD8+ T cell migration and activation by Flightless-1
Flightless-1 控制 CD8 T 细胞迁移和激活
- 批准号:
10155177 - 财政年份:2021
- 资助金额:
$ 21.76万 - 项目类别:
Mechanisms of autoimmune disease risk in IL2/IL2RA-dependent immune tolerance
IL2/IL2RA依赖性免疫耐受中自身免疫性疾病风险的机制
- 批准号:
10358624 - 财政年份:2021
- 资助金额:
$ 21.76万 - 项目类别:
Mechanisms of autoimmune disease risk in IL2/IL2RA-dependent immune tolerance
IL2/IL2RA依赖性免疫耐受中自身免疫性疾病风险的机制
- 批准号:
10553203 - 财政年份:2021
- 资助金额:
$ 21.76万 - 项目类别:
Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
特殊 CD4 T 细胞群对皮肤免疫和组织修复的调节
- 批准号:
9384627 - 财政年份:2017
- 资助金额:
$ 21.76万 - 项目类别:
Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
特殊 CD4 T 细胞群对皮肤免疫和组织修复的调节
- 批准号:
9926223 - 财政年份:2017
- 资助金额:
$ 21.76万 - 项目类别:
Targeting the IL-2/regulatory T cell axis for autoimmune disease prevention in realistic animal models
靶向 IL-2/调节性 T 细胞轴在真实动物模型中预防自身免疫性疾病
- 批准号:
10307124 - 财政年份:2017
- 资助金额:
$ 21.76万 - 项目类别:
Targeting the IL-2/regulatory T cell axis for autoimmune disease prevention in realistic animal models
靶向 IL-2/调节性 T 细胞轴在真实动物模型中预防自身免疫性疾病
- 批准号:
10062808 - 财政年份:2017
- 资助金额:
$ 21.76万 - 项目类别:
Control of CD8+ T cell activation and differentiation by the signaling adaptor BCAP
信号适配器 BCAP 控制 CD8 T 细胞活化和分化
- 批准号:
9177685 - 财政年份:2016
- 资助金额:
$ 21.76万 - 项目类别:
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