Molecular Mechanisms of Invariant Natural Killer T Cell Differentiation

恒定自然杀伤T细胞分化的分子机制

• 批准号: 10627307
• 负责人: BARBARA L. KEE
• 金额: $ 32.47万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10627307
• 关键词: Adhesions; Anatomy; Antibodies; Autoimmune Hepatitis; Bacterial Infections; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Adhesion; Cell Differentiation process; Cell Maturation; Cell physiology; Cells; Chromatin; Confocal Microscopy; Cytotoxic T-Lymphocytes; Data; Dendritic cell activation; Development; Disease; Frequencies; Future; Gene Expression; Genes; Genetic Transcription; Genus Mycobacterium; Glycolipids; Grant; Hepatitis; Heterogeneity; Human; Immune; Immunofluorescence Immunologic; Immunotherapeutic agent; Interferon Type II; Invaded; Ligands; Liver; Location; Lymphocyte; Lymphoid; Lymphoid Cell; Mediating; Memory; Molecular; Mucous Membrane; Mus; NK Cell Activation; Natural Killer Cells; Pathway interactions; Peripheral; Play; Process; Property; Regulation; Residencies; Role; Sentinel; Spleen; T cell differentiation; T memory cell; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; Therapeutic; Thymic epithelial cell; Thymus Gland; Tissues; Transposase; cell type; cytokine; cytotoxicity; design; epithelial to mesenchymal transition; experimental study; in vivo; insight; migration; mouse model; novel; pathogen; programs; response; single-cell RNA sequencing; trafficking; transcription factor; tumor

Project Summary Invariant Natural Killer T (iNKT) cells are T lymphocytes that express a semi-invariant T cell receptor (TCR) and exist in a primed effector state capable of making numerous cytokines within minutes after activation. iNKT1 cells develop in the thymus and migrate as immature cells to peripheral lymphoid and non-lymphoid organs where they reside as tissue-resident sentinels that protect against invading pathogens. Here we describe the transcription factor Ets1 as a central regulator of the development, adhesion, migration, and NK cell-associated gene programs of iNKT1 cells that control their tissue residency, localization, and function. We propose experiments to investigate the relevance of these programs to iNKT1 cell development, trafficking, location and function as well as experiments to identify the molecular basis for Ets1- mediated regulation of these programs in the thymus, liver and spleen. Given the conservation of tissue residency and adhesion programs across lymphocytes, we propose that our data will provide not only significant insight into the mechanisms controlling iNKT1 cell location but also in other innate and adaptive lymphocytes.

项目摘要 不变自然杀伤T（iNKT）细胞是表达半不变T细胞的T淋巴细胞， 受体（TCR），并以能够产生多种细胞因子的引发效应状态存在 在激活后的几分钟内。iNKT 1细胞在胸腺中发育并作为未成熟细胞迁移 转移到外周淋巴和非淋巴器官，作为组织驻留哨兵 抵御入侵的病原体。在这里，我们将转录因子Ets1描述为 发育、粘附、迁移和NK细胞相关基因的中枢调节因子 iNKT 1细胞的程序，控制其组织驻留，定位和功能。我们 提出实验来研究这些程序与iNKT 1细胞发育的相关性， 运输，位置和功能，以及实验，以确定Ets 1的分子基础， 介导的调节这些程序在胸腺，肝脏和脾脏。考虑到 的组织驻留和粘附程序跨越淋巴细胞，我们建议，我们的数据将 不仅为控制iNKT 1细胞定位的机制提供了重要的见解， 在其他先天和适应性淋巴细胞中。