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
基本信息
- 批准号:9247132
- 负责人:
- 金额:$ 25.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:Adaptive Immune SystemAntigen ReceptorsAntigensAreaBone MarrowC57BL/6 MouseCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCategoriesCell Differentiation processCellsCharacteristicsChimera organismClinicalCommon Lymphoid ProgenitorCytotoxic T-LymphocytesDNA BindingDevelopmentDominant-Negative MutationE proteinEDN2 geneEndothelin-2FamilyFlow CytometryGenerationsGeneticGenetic RecombinationGenetic TranscriptionGerm LinesGoalsHelper-Inducer T-LymphocyteHematopoietic stem cellsImmune responseImmune systemInbred BALB C MiceInfectionInnate Immune SystemLiverLungLymphocyteLymphoidLymphoid CellMaintenanceMemoryMethodsModelingMolecularMouse StrainsMusMyelogenousNatural Killer CellsOrganismPathologyPatternPlayPopulationProductionPropertyProtein FamilyRag1 MouseRegulationResearchRoleSiteSpleenSubfamily lentivirinaeSystemT-LymphocyteTestingThymus GlandTimeTransgenic Micearmbaseexperimental studyhelix-loop-helix protein differentiation inhibitorinhibitor/antagonistinterestlymph nodesnovel strategiespathogenprogenitorprogramsprotein Epublic health relevancereceptorresponsethymocytetranscription factor
项目摘要
DESCRIPTION (provided by applicant): Classically the immune system has been divided into adaptive and innate systems, differentiated by the use of clonally-specific antigen-specific receptors generated by genetic recombination vs. non-diverse receptors that recognize evolutionary conserved pathogen molecules. The former requires more time to mount an effective response, but has memory, while the latter responds rapidly, and has no memory. Most components of the innate immune system derive from myeloid precursors, while the adaptive immune system derives from lymphoid precursors. However, there are a number of lymphoid cells that straddle these categories. The classic example are NK cells, lymphocytes that develop from CLPs but recognize pathogen using germ line-encoded receptors and exist in a primed state. In the last few year an increasing number of other innate lymphoid cells have been identified, including ILCs (innate lymphoid cells), as well as some cells that express rearranged antigen receptors, such as NKTs, and some T cells. The roles and significance of these populations in normal immune responses and pathology is an underexplored area of great interest. Some of these innate lymphoid cells, especially ILCs and NKTs share developmental and effector programs with conventional helper T cells. The Th1, Th2, and Th17 programs share properties with the ILC1, ILC2, ILC3 and the NKT1, NKT2, and NKT17 programs, respectively. Since different mouse strains have significantly different distributions of
these lineages, it is clear that genetic factors contribute to the differentiation across these alternative effector fates, but the molecular mechanisms that determine the representation of each effector type within each population are unknown, as is whether these mechanisms are common for the different lineages. Recent experiments from our group suggest that changes in E protein activity in developing NKT cells substantially bias effector lineage differentiation. Increasing E protein activity in C57BL/6 thymocytes results in a change from a predominant NKT1 differentiation profile to a NKT2/NKT17 profile. In this project we will 1) test this model by
trying to convert the predominant NKT2 differentiation pattern in Balb/c mice to NKT1 by decreasing E protein activity in DP thymocytes. 2) analyze whether E protein activity plays a similar role during ILC differentiation.
描述(申请人提供):传统上,免疫系统被分为适应性和先天系统,通过使用由基因重组产生的克隆特异性抗原特异性受体和识别进化保守的病原体分子的非多样性受体来区分。前者需要更多的时间来建立有效的反应,但有记忆力,而后者反应迅速,没有记忆力。天然免疫系统的大部分成分来自髓系前体,而获得性免疫系统来自淋巴系前体。然而,有一些淋巴样细胞横跨这些类别。经典的例子是NK细胞,这种淋巴细胞从CLP发育而来,但使用生殖线编码的受体识别病原体,并以启动状态存在。在过去的几年里,越来越多的其他固有淋巴样细胞被发现,包括ILCs(固有淋巴样细胞),以及一些表达重排抗原受体的细胞,如NKT和一些T细胞。这些群体在正常免疫反应和病理中的作用和意义是一个未被充分研究的领域。其中一些先天淋巴样细胞,特别是ILCs和NKT,与传统的辅助T细胞共享发育和效应程序。Th1、Th2和Th17程序分别与ILC1、ILC2、ILC3和NKT1、NKT2和NKT17程序共享属性。由于不同品系的小鼠具有显著不同的分布
对于这些谱系,很明显,遗传因素有助于这些不同效应器命运的分化,但决定每个种群中每种效应器类型的代表的分子机制尚不清楚,以及这些机制是否在不同的谱系中是共同的。我们小组最近的实验表明,发育中的NKT细胞中E蛋白活性的变化实质上会影响效应细胞的谱系分化。C57BL/6胸腺细胞中E蛋白活性的增加导致从主要的NKT1分化谱转变为NKT2/NKT17谱。在这个项目中,我们将1)通过以下方式测试此模型
试图通过降低胸腺细胞中E蛋白的活性,将Balb/c小鼠主要的NKT2分化模式转变为NKT1。2)分析E蛋白活性在ILC分化过程中是否起类似作用。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Development of Type 2 Innate Lymphoid Cells Is Selectively Inhibited by Sustained E Protein Activity.
- DOI:10.4049/immunohorizons.1900045
- 发表时间:2019-12-18
- 期刊:
- 影响因子:0
- 作者:Berrett, Hannah;Qian, Liangyue;Alberola-Ila, Jose
- 通讯作者:Alberola-Ila, Jose
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jose Alberola-Ila其他文献
Jose Alberola-Ila的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
$ 25.73万 - 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:
9900716 - 财政年份:2018
- 资助金额:
$ 25.73万 - 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:
$ 25.73万 - 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:
$ 25.73万 - 项目类别:
相似海外基金
Development of back bone vectors for chimeric antigen receptors against key molecules, CD47 and CD24, activating macrophages
开发针对关键分子 CD47 和 CD24 的嵌合抗原受体的骨干载体,激活巨噬细胞
- 批准号:
23K06728 - 财政年份:2023
- 资助金额:
$ 25.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Engineering synthetic adhesion receptors to enhance the sensitivity of therapeutic chimeric antigen receptors
工程合成粘附受体以增强治疗性嵌合抗原受体的敏感性
- 批准号:
MR/W031353/1 - 财政年份:2022
- 资助金额:
$ 25.73万 - 项目类别:
Research Grant
CAREER: Engineering next-generation chimeric antigen receptors for cancer immunotherapy using phospho-proteomics
职业:利用磷酸蛋白质组学设计用于癌症免疫治疗的下一代嵌合抗原受体
- 批准号:
2145853 - 财政年份:2022
- 资助金额:
$ 25.73万 - 项目类别:
Continuing Grant
Construction of a drug discovery platform utilizing antigen receptors that regulate the quality of cancer immunity
利用调节癌症免疫质量的抗原受体构建药物发现平台
- 批准号:
22K06603 - 财政年份:2022
- 资助金额:
$ 25.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Modeling based design of chimeric antigen receptors for Natural Killer cell-based immunotherapy
用于基于自然杀伤细胞的免疫治疗的嵌合抗原受体的基于建模的设计
- 批准号:
10701754 - 财政年份:2022
- 资助金额:
$ 25.73万 - 项目类别:
Modeling based design of chimeric antigen receptors for Natural Killer cell-based immunotherapy
用于基于自然杀伤细胞的免疫治疗的嵌合抗原受体的基于建模的设计
- 批准号:
10557760 - 财政年份:2022
- 资助金额:
$ 25.73万 - 项目类别:
Molecualr imaging for development of chimeric antigen receptors (CARs) resistant to T cell exhaustion
用于开发抗 T 细胞耗竭的嵌合抗原受体 (CAR) 的分子成像
- 批准号:
20H03536 - 财政年份:2020
- 资助金额:
$ 25.73万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Chimeric antigen receptors on regulatory T cells as a treatment strategy in auto-immune diseases.
调节性 T 细胞上的嵌合抗原受体作为自身免疫性疾病的治疗策略。
- 批准号:
437200 - 财政年份:2020
- 资助金额:
$ 25.73万 - 项目类别:
Studentship Programs
Therapeutic Anti-HIV Chimeric Antigen Receptors Via Stem Cell Delivery
通过干细胞递送治疗性抗 HIV 嵌合抗原受体
- 批准号:
10542442 - 财政年份:2020
- 资助金额:
$ 25.73万 - 项目类别:
Therapeutic Anti-HIV Chimeric Antigen Receptors Via Stem Cell Delivery
通过干细胞递送治疗性抗 HIV 嵌合抗原受体
- 批准号:
9922602 - 财政年份:2020
- 资助金额:
$ 25.73万 - 项目类别:














{{item.name}}会员




