Bidirectional metabolic signaling in follicular helper T cell differentiation
滤泡辅助 T 细胞分化中的双向代谢信号
基本信息
- 批准号:10687027
- 负责人:
- 金额:$ 53.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-19 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Activated LymphocyteAffinityAmino AcidsAntibody AffinityAntibody FormationAntigensAutoimmune DiseasesB-LymphocytesBiologicalBiologyCell physiologyCellsCellular ImmunityDefectDistalFRAP1 geneFeedsGTP-Binding ProteinsGeneticGenetic ModelsGenetic ScreeningGenetic TranscriptionGlycolysisGrowthGuanosine Triphosphate PhosphohydrolasesHelper-Inducer T-LymphocyteHeterogeneityHomologous GeneHumoral ImmunitiesImmune System DiseasesImmune signalingImmunoglobulinsImmunologic ReceptorsInvadedKnowledgeLinkMediatingMetabolicMetabolic PathwayMetabolismMitochondriaModelingMonomeric GTP-Binding ProteinsMusNutrientOxidative PhosphorylationPathway interactionsPhenotypePost-Translational Protein ProcessingProcessProteinsProteomicsRegulationRoleShapesSignal PathwaySignal TransductionStructure of germinal center of lymph nodeSystemic Lupus ErythematosusSystems BiologyT cell differentiationT cell responseT-Cell ActivationT-Cell ReceptorT-LymphocyteTestingTh1 CellsTherapeuticTranslatingUp-Regulationamino acid metabolismeffector T cellfatty acid biosynthesisglucose metabolismin vivoinnovationinsightinterestmetabolomemitochondrial metabolismmouse geneticsnovelpathogenprogramsreceptorresponsescreeningsingle-cell RNA sequencingtranscription factor
项目摘要
Program Summary/Abstract
Follicular helper T (Tfh) cells provide essential help for B cells and high-affinity antibody production, thereby
linking cellular and humoral immunity. While much emphasis has been placed on immune receptors (e.g.
ICOS) and transcription factors (e.g. Bcl6) required for Tfh differentiation, how signals are transduced from
receptors to transcriptional and biological responses remains poorly defined. Emerging studies reveal nutrient
signaling and metabolic reprogramming as fundamental processes underlying the growth and fate decisions of
activated lymphocytes. However, many questions remain regarding the specific metabolic pathways important
for T cell fate decisions (rather than as a consequence of changes in cellular phenotypes), and how immune
signals intersect with nutrient inputs and metabolic programs. For instance, compared with our knowledge on
glycolytic or Warburg metabolism, the function and regulation of mitochondrial metabolism are much less clear.
We establish that mTOR acts as a key driver of Tfh differentiation by coordinating T cell receptor and ICOS
signaling and glucose metabolism. Through unbiased screens, mouse genetic models and systems biology
approaches in our preliminary studies, we also revealed crucial roles of nutrient signaling and mitochondrial
metabolism in Tfh responses. Our central hypothesis is that the interplay between mTORC1 and nutrient
signaling pathways and mitochondrial metabolic programs orchestrates bidirectional metabolic
signaling and Tfh differentiation. Specifically, we will (1) identify the mechanisms that integrate nutrient and
immune signals in Tfh responses, and (2) establish mitochondrial function and metabolic heterogeneity in Tfh
responses. Importantly, despite the emerging interest in immunometabolism, how nutrient signaling and
mitochondrial metabolism contribute to T cell function remains poorly understood. Building upon our expertise
and innovation that combine genetic and systems biology approaches, we will address fundamental questions
of immunometabolism and Tfh biology. Insights gained from this application may significantly impact our
understanding of Tfh biology and manifest legitimate therapeutic opportunities.
程序总结/文摘
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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Hongbo Chi其他文献
Hongbo Chi的其他文献
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Integrating systems immunology with immunometabolism and cancer immunity
将系统免疫学与免疫代谢和癌症免疫相结合
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$ 53.63万 - 项目类别:
Bidirectional metabolic signaling in follicular helper T cell differentiation
滤泡辅助 T 细胞分化中的双向代谢信号
- 批准号:
10020901 - 财政年份:2019
- 资助金额:
$ 53.63万 - 项目类别:
Bidirectional metabolic signaling in follicular helper T cell differentiation
滤泡辅助 T 细胞分化中的双向代谢信号
- 批准号:
10466976 - 财政年份:2019
- 资助金额:
$ 53.63万 - 项目类别:
Bidirectional metabolic signaling in follicular helper T cell differentiation
滤泡辅助 T 细胞分化中的双向代谢信号
- 批准号:
10231172 - 财政年份:2019
- 资助金额:
$ 53.63万 - 项目类别:
Bidirectional metabolic signaling in follicular helper T cell differentiation
滤泡辅助 T 细胞分化中的双向代谢信号
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9917280 - 财政年份:2019
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