Characterization of a distinct NKT subset and its role in influenza responses
独特 NKT 亚群的特征及其在流感反应中的作用
基本信息
- 批准号:9900716
- 负责人:
- 金额:$ 53.79万
- 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:2018-05-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAdoptive TransferAffectAntigensBody Weight decreasedCD8-Positive T-LymphocytesCellsCytotoxic T-LymphocytesDevelopmentE proteinEndothelin-2EpithelialEpitheliumExpression ProfilingFamilyFutureGene ExpressionGenerationsGenetic ModelsHelper-Inducer T-LymphocyteHoming BehaviorHumanImmuneImmune responseImmunityIn VitroInfectionInflammationInflammatoryInfluenzaInfluenza A virusInhibitor of Differentiation ProteinsInterleukin-10LipidsLungMalignant NeoplasmsMediastinalModelingMolecularMorbidity - disease rateMouse StrainsMusOrganOutcomePathway interactionsPhysiologicalPlayPopulationProcessProductionPropertyPublic HealthRecoveryReportingRoleSuppressor-Effector T-LymphocytesT cell responseT-Cell DevelopmentT-LymphocyteT-Lymphocyte SubsetsTestingTreatment outcomeVaccinationVaccinesVirus DiseasesWild Type Mousealveolar epitheliumbasecancer therapychemokinecytokineeosinophilexperimental studyfluimprovedimproved outcomein vivoinfluenza virus vaccineinfluenzavirusinterestinterleukin-22lymph nodesmigrationmonocytemortalitymouse modelnovelpathogenprogramsrecruitresponsetranscription factortranscriptome sequencing
项目摘要
ABSTRACT
Invariant natural killer T cells (NKT cells) are a conserved T cell population that behaves
like innate cells, rapidly secreting cytokines when stimulated. Different subsets of iNKT cells
have been reported, including NKT1, NKT2 and NKT17 cells, similar to TH1, TH2 and TH17
cells. The relationships between the different subsets, their stability, and their functional
relevance remain incompletely characterized. We have shown in a mouse model (ET-2) that
a small alteration in E protein activity during development results in a dramatic change in the
differentiation profile of iNKTs, with a decrease in NKT1s and an increase in other subsets,
including a novel type. This model provides a unique opportunity to test the impact of
different NKT populations in normal immune responses. We chose to test the possible
impact of these changes in NKT cells on the immune response to flu, given the relevance of
flu as a public health problem and the fact that activation of NKT cells has been successfully
used as a novel adjuvant to increase vaccination efficiency. Preliminary results show that
ET-2 mice have better outcomes to influenza challenge, and that this correlates with
increased numbers a novel NKT subset in the mediastinal LN. In this proposal we will first
characterize functionally and molecularly this novel NKT subset, and then use the
information to extend our preliminary studies on influenza responses, testing the impact of
these cells on different aspects of the immune response where iNKT cells have been
implicated, namely recruitment of inflammatory monocytes, production of IL-22, activation of
ILC2 and subsequently recruitment of eosinophils, generation of adaptive CD4 and CD8 T
cell responses to viral infections, and decreased epithelial damage in the course of the
infection. The comparison of the responses of the iNKT present in WT mice with those in
ET-2 mice at these different stages of the immune response will facilitate a mechanistic
understanding of the physiological role of NKT cells during influenza infection. The results
from these experiments will characterize a novel subset of iNKT cells that could be very
relevant for immune responses against flu and other pathogens, and increase our
understanding of the physiological role of iNKTs during immune responses to flu. Given the
interest in using activation of iNKTs as an adjuvant in flu vaccines or in different cancer
therapies, these studies could inform future strategies to selectively activate only those NKT
subsets that favor the desired outcome of the treatment.
摘要
不变的自然杀伤T细胞(NKT细胞)是一种保守的T细胞群,表现为
就像先天细胞一样,在受到刺激时会迅速分泌细胞因子。INKT细胞的不同亚群
已报道包括NKT1、NKT2和NKT17细胞,与TH1、TH2和TH17细胞相似
细胞。不同子集之间的关系、它们的稳定性和它们的功能
相关性仍然是不完全的特征。我们已经在小鼠模型(ET-2)中证明了
在发育过程中,E蛋白活性的微小变化会导致
INKT的分化特征,NKT1减少,其他亚群增加,
包括一种新奇的类型。该模型提供了一个独特的机会来测试
不同的NKT人群在正常免疫反应中。我们选择测试可能的
NKT细胞的这些变化对流感免疫反应的影响,考虑到
流感是一个公共卫生问题,NKT细胞的激活已经成功
作为一种新型佐剂用于提高疫苗接种效率。初步结果显示,
ET-2小鼠对流感的攻击有更好的结果,这与
在纵隔LN中增加了一个新的NKT亚群.在这项提议中,我们将首先
从功能和分子上表征这个新的NKT子集,然后使用
扩大我们对流感反应的初步研究的信息,测试
这些细胞在免疫反应的不同方面,iNKT细胞
即炎性单核细胞的募集,IL-22的产生,
ILC2和随后的嗜酸性粒细胞招募,产生适应性的CD4和CD8T
细胞对病毒感染的反应,并减少在感染过程中的上皮损伤
感染。WT小鼠体内iNKT免疫应答的比较
ET-2小鼠在这些不同的免疫反应阶段将促进一种机制
了解NKT细胞在流感感染中的生理作用。结果是
将描述一种新的iNKT细胞子集,它可能非常
与对抗流感和其他病原体的免疫反应有关,并增加我们的
了解iNKT在流感免疫反应中的生理作用。给定
有兴趣将激活的iNKT用作流感疫苗或不同癌症的佐剂
治疗,这些研究可以为未来的策略提供信息,选择性地激活那些NKT
有利于预期治疗结果的子集。
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)
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Jose Alberola-Ila其他文献
Jose Alberola-Ila的其他文献
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{{ truncateString('Jose Alberola-Ila', 18)}}的其他基金
Characterization of a distinct NKT subset and its role in influenza responses
独特 NKT 亚群的特征及其在流感反应中的作用
- 批准号:
10392859 - 财政年份:2018
- 资助金额:
$ 53.79万 - 项目类别:
Characterization of a distinct NKT subset and its role in influenza responses
独特 NKT 亚群的特征及其在流感反应中的作用
- 批准号:
10132967 - 财政年份:2018
- 资助金额:
$ 53.79万 - 项目类别:
E protein activity regulates effector lineage differentiation of NKT and ILCs
E蛋白活性调节NKT和ILC的效应谱系分化
- 批准号:
9247132 - 财政年份:2016
- 资助金额:
$ 53.79万 - 项目类别:
Regulation of NKT cell development and function by c-Myb
c-Myb 对 NKT 细胞发育和功能的调节
- 批准号:
8032491 - 财政年份:2010
- 资助金额:
$ 53.79万 - 项目类别:
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