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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要不变自然杀伤 T (iNKT) 细胞是表达半不变 T 细胞的 T 淋巴细胞受体（TCR）并以启动效应子状态存在，能够产生大量细胞因子激活后几分钟内。 iNKT1 细胞在胸腺中发育并作为未成熟细胞迁移外周淋巴和非淋巴器官作为组织驻留哨兵防止病原体入侵。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 iNKT1 细胞控制其组织驻留、定位和功能的程序。我们提出实验来研究这些程序与 iNKT1 细胞发育的相关性，运输、定位和功能以及确定 Ets1- 分子基础的实验介导调节胸腺、肝脏和脾脏中的这些程序。鉴于保护淋巴细胞的组织驻留和粘附程序，我们建议我们的数据将不仅提供了对控制 iNKT1 细胞定位的机制的重要见解，而且在其他先天性和适应性淋巴细胞中。