Signals that Control Thymocyte Migration

控制胸腺细胞迁移的信号

• 批准号: 10753064
• 负责人: ELLEN A ROBEY
• 金额: $ 46.76万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-18 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753064
• 关键词: Adopted; Binding; CD4 Positive T Lymphocytes; CD8B1 gene; Calcineurin; Cell Fate Control; Cells; Data; Genetic Transcription; Helper-Inducer T-Lymphocyte; Killer Cells; Lead; Ligands; Link; Literature; MEKs; Mammalian Cell; Maps; Modeling; Molecular; Outcome; Pathway interactions; Peptide/MHC Complex; Peptides; Phase; Publishing; Resolution; Role; Shapes; Signal Pathway; Signal Transduction; Specific qualifier value; T-Cell Development; T-Lymphocyte; Testing; Thymus Gland; Time; Transcriptional Regulation; adaptive immune response; effector T cell; gene induction; migration; multiple omics; nuclear factors of activated T-cells; programs; thymocyte; transcription factor

Abstract: The choice of developing T cells to adopt the CD4 helper or CD8 killer cell fate is a valuable model for understanding mammalian cell fate decisions and is a key step in shaping the adaptive immune response. While it is known that TCR recognition of self pMHC ligands in the thymus controls cell fate, the molecular links between TCR signaling and the activation of the lineage-defining transcriptional networks remains unknown. Guided by a high-resolution single cell map of T cell development, we propose to define the molecular links between different branches of the TCR signaling pathway and the transcriptional network that specifies the CD4 fate (Aim 1). We will also probe the factors that determine why thymocytes that recognize MHC-2 fully activate this network, whereas thymocytes that recognize MHC-1 do not (Aim 2). The proposed studies will reveal fundamental principles underlying mammalian cell fate decisions and help to understand the molecular mechanisms that link the killer versus helper T cell effector functional programs to the recognition of MHC 1 versus 2.

抽象的： 开发T细胞采用CD4助手或CD8杀手细胞命运的选择是一个有价值的模型 了解哺乳动物的细胞命运决策，是塑造适应性免疫反应的关键步骤。 虽然众所周知，胸腺中对自我PMHC配体的TCR识别控制细胞命运，但分子 TCR信号传导与谱系定义转录网络的激活之间的联系 未知。在T细胞发育的高分辨率单细胞图的指导下，我们建议定义 TCR信号通路和转录网络之间不同分支之间的分子链接 这指定了CD4命运（AIM 1）。我们还将探测确定为什么胸腺细胞的因素 识别MHC-2充分激活该网络，而识别MHC-1的胸腺细胞不能（AIM 2）。这 拟议的研究将揭示哺乳动物细胞命运决定的基本原理，并有助于帮助 了解将杀手与助手T细胞效应程序功能程序与助手T细胞效应程序联系起来的分子机制 MHC 1对2的识别。

项目成果

Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ.

• DOI: 10.1126/scisignal.2004400
• 发表时间: 2013-10-15
• 期刊: Science signaling
• 影响因子: 7.3
• 作者: Melichar HJ;Ross JO;Herzmark P;Hogquist KA;Robey EA
• 通讯作者: Robey EA

Thymic macrophages consist of two populations with distinct localization and origin.

• DOI: 10.7554/elife.75148
• 发表时间: 2022-11-30
• 期刊: eLife
• 影响因子: 7.7
• 作者: Zhou TA;Hsu HP;Tu YH;Cheng HK;Lin CY;Chen NJ;Tsai JW;Robey EA;Huang HC;Hsu CL;Dzhagalov IL
• 通讯作者: Dzhagalov IL

Regulation of thymocyte positive selection and motility by GIT2.

• DOI: 10.1038/ni.1868
• 发表时间: 2010-06
• 期刊: Nature immunology
• 影响因子: 30.5

Conserved and divergent aspects of human T-cell development and migration in humanized mice.

• DOI: 10.1038/icb.2015.38
• 发表时间: 2015-09
• 期刊: Immunology and cell biology
• 影响因子: 4
• 作者: Halkias J;Yen B;Taylor KT;Reinhartz O;Winoto A;Robey EA;Melichar HJ
• 通讯作者: Melichar HJ