Development of follicular helper T cell deficient mice
滤泡辅助性T细胞缺陷小鼠的发育
基本信息
- 批准号:8522152
- 负责人:
- 金额:$ 22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-08-03 至 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAffinityAntibodiesAntibody FormationAntigensAutoantibodiesAutoimmunityB-LymphocytesBCL6 geneBLR1 geneBreedingCD4 Positive T LymphocytesCell Differentiation processCell LineageCell physiologyCellsCommunicable DiseasesDefectDevelopmentDiseaseGene TargetingGenerationsHelper-Inducer T-LymphocyteImmune responseIn VitroKnockout MiceLeadMusMutatePhenotypeProductionReactionRegulatory T-LymphocyteRoleStagingStructure of germinal center of lymph nodeStudy modelsSystemSystems AnalysisT cell differentiationT-Cell DevelopmentT-LymphocyteTestingThymus GlandTranscription Repressor/CorepressorTransgenic MiceTransgenic ModelTransgenic Organismsbiological systemscell typechemokine receptorcytokinefightingimprovedin vivoinnovationinsightmouse modelnovelprogramsresearch studytoolvaccine development
项目摘要
DESCRIPTION (provided by applicant): CD4 T helper cells are critical for the proper function of the immune response and are essential for helping B cells make high affinity antigen-specific antibody. Follicular helper T (Tfh) cells are a recently characterized subset of CD4 T cells whose role is specifically to help B cells produce antibody, in part by promoting the germinal center reaction. In the absence of Tfh cells, germinal centers and secondary antibody responses fail to develop. Excessive development of Tfh cells can lead to autoimmunity. Tfh cells are localized to B cell follicles due to their expression of the chemokine receptor CXCR5. Tfh cells are also characterized by high expression of the transcription repressor BCL6, and secretion of the B cell stimulatory cytokine IL-21. Recent studies have shown that BCL6 is the master transcriptional regulator for Tfh cells: forced BCL6 expression can induce a Tfh phenotype in T cells, and Tfh cells cannot develop in the absence of BCL6. However, what is lacking for the study of Tfh cells is a convenient in vivo system for analyzing the function of Tfh cells. While BCL6 knockout mice lack Tfh cells, they also have a large number of other defects and are difficult to breed. We are currently developing mice in which BCL6 is specifically mutated in CD4 T cells. We propose that this mouse model will be highly useful and vastly improved model for the study of Tfh cell function. Furthermore, this mouse will provide essential and final confirmation that Tfh cells are intrinsically dependent upon BCL6 for their development. INNOVATION: This study uses a completely novel mouse model to analyze Tfh cell function. Additionally, we propose to develop an innovative transgenic mouse that can be used to track the Tfh cell fate. Overall, these experiments will give insights into the development of Tfh cells and will lead to the development of a critical new tool for studying Tfh cell function. IMPACT: These experiments will provide information that is critical for understanding the development of the antibody response to fight infectious disease. These studies should also accelerate the development of vaccines that target Tfh cells, as well as impact studies on autoantibody production.
描述(由申请方提供):CD 4 T辅助细胞对于免疫应答的正常功能至关重要,并且对于帮助B细胞产生高亲和力抗原特异性抗体至关重要。滤泡辅助性T(Tfh)细胞是最近表征的CD 4 T细胞亚群,其作用是特异性地帮助B细胞产生抗体,部分通过促进生发中心反应。在缺乏Tfh细胞的情况下,生发中心和二次抗体反应不能发展。Tfh细胞的过度发育可导致自身免疫。Tfh细胞由于其表达趋化因子受体CXCR 5而定位于B细胞滤泡。Tfh细胞的特征还在于转录阻遏物BCL 6的高表达和B细胞刺激性细胞因子IL-21的分泌。最近的研究表明,BCL 6是Tfh细胞的主要转录调节因子:强制BCL 6表达可以诱导T细胞中的Tfh表型,并且Tfh细胞在没有BCL 6的情况下不能发育。然而,Tfh细胞的研究缺乏的是用于分析Tfh细胞功能的方便的体内系统。虽然BCL 6基因敲除小鼠缺乏Tfh细胞,但它们也有大量其他缺陷,难以繁殖。我们目前正在开发小鼠,其中BCL 6在CD 4 T细胞中特异性突变。我们建议,这种小鼠模型将是非常有用的,大大改善模型的研究Tfh细胞的功能。此外,该小鼠将提供Tfh细胞内在地依赖于BCL 6以用于其发育的基本和最终确认。创新:这项研究使用了一种全新的小鼠模型来分析Tfh细胞功能。此外,我们建议开发一种创新的转基因小鼠,可用于跟踪Tfh细胞的命运。总的来说,这些实验将深入了解Tfh细胞的发育,并将导致研究Tfh细胞功能的关键新工具的开发。影响:这些实验将提供信息,这是了解抗体反应的发展,以打击传染病的关键。这些研究还应该加速靶向Tfh细胞的疫苗的开发,以及对自身抗体产生的影响研究。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
An Inhibitory Role for the Transcription Factor Stat3 in Controlling IL-4 and Bcl6 Expression in Follicular Helper T Cells.
- DOI:10.4049/jimmunol.1500335
- 发表时间:2015-09-01
- 期刊:
- 影响因子:0
- 作者:Wu H;Xu LL;Teuscher P;Liu H;Kaplan MH;Dent AL
- 通讯作者:Dent AL
Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice.
- DOI:10.1002/eji.201546094
- 发表时间:2016-05
- 期刊:
- 影响因子:5.4
- 作者:Wu H;Chen Y;Liu H;Xu LL;Teuscher P;Wang S;Lu S;Dent AL
- 通讯作者:Dent AL
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Alexander L Dent其他文献
Lipids-Я-Us: peroxisome generation of iNKT ligands
脂质-我-我们:iNKT 配体的过氧化物酶体生成
- DOI:
10.1038/ni.2288 - 发表时间:
2012-04-18 - 期刊:
- 影响因子:27.600
- 作者:
Randy R Brutkiewicz;Alexander L Dent - 通讯作者:
Alexander L Dent
Alexander L Dent的其他文献
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{{ truncateString('Alexander L Dent', 18)}}的其他基金
Control of ST2+ Treg Development in Allergic Disease by Bcl6 and Sex Hormone Receptors
Bcl6 和性激素受体控制过敏性疾病中 ST2 Treg 的发育
- 批准号:
10633229 - 财政年份:2022
- 资助金额:
$ 22万 - 项目类别:
Control of ST2+ Treg Development in Allergic Disease by Bcl6 and Sex Hormone Receptors
Bcl6 和性激素受体控制过敏性疾病中 ST2 Treg 的发育
- 批准号:
10535286 - 财政年份:2022
- 资助金额:
$ 22万 - 项目类别:
The control of allergic immune responses by follicular regulatory T cells
滤泡调节性 T 细胞对过敏性免疫反应的控制
- 批准号:
10165474 - 财政年份:2017
- 资助金额:
$ 22万 - 项目类别:
The Role of Follicular Helper T Cells in HIV Prime Boost Vaccination
滤泡辅助 T 细胞在 HIV 加强疫苗接种中的作用
- 批准号:
8875819 - 财政年份:2014
- 资助金额:
$ 22万 - 项目类别:
Regulation of Follicular Helper T cell Differentiation and Vaccination by IL3
IL3 对滤泡辅助 T 细胞分化和疫苗接种的调节
- 批准号:
8853812 - 财政年份:2014
- 资助金额:
$ 22万 - 项目类别:
Regulation of Follicular Helper T cell Differentiation and Vaccination by IL3
IL3 对滤泡辅助 T 细胞分化和疫苗接种的调节
- 批准号:
8681872 - 财政年份:2014
- 资助金额:
$ 22万 - 项目类别:
Control of airway inflammation and Th2 differentiation by microRNA 21
microRNA 控制气道炎症和 Th2 分化 21
- 批准号:
8434965 - 财政年份:2012
- 资助金额:
$ 22万 - 项目类别:
Development of follicular helper T cell deficient mice
滤泡辅助性T细胞缺陷小鼠的发育
- 批准号:
8289751 - 财政年份:2012
- 资助金额:
$ 22万 - 项目类别:
Control of autoimmunity by follicular helper T cells and BCL6
滤泡辅助 T 细胞和 BCL6 控制自身免疫
- 批准号:
8072744 - 财政年份:2010
- 资助金额:
$ 22万 - 项目类别:
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