E and Id protein function in natural killer T cell differentiation

E 和 Id 蛋白在自然杀伤 T 细胞分化中的功能

基本信息

批准号：
8735243
负责人：
BARBARA L. KEE
金额：
$ 36.61万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-24 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8735243
关键词：
Address Affinity Antigens Applications Grants Asthma Atherosclerosis Autoimmune Diseases Autoimmunity B-Lymphocytes BHLH Protein Binding Binding Sites Bone Marrow Boxing CD8B1 gene Cell Differentiation process Cell Lineage Cell physiology Cells Characteristics Data Development Disease Dose E protein Effector Cell Event Failure Fatty acid glycerol esters Foundations Frequencies Gene Targeting Germ Lines Glycolipids Goals Grant Helper-Inducer T-Lymphocyte Hypersensitivity Immune Immune response Immune system Infection Insulin-Dependent Diabetes Mellitus Interleukin-4 Lead Lymphocyte Lymphocyte Subset Lymphoid Cell Malignant Neoplasms Memory Molecular Multiple Sclerosis Mus Mycobacterium tuberculosis Natural Killer Cells Phenotype Play Population Predisposition Process Protein Binding Proteins Regulation Research Rheumatoid Arthritis Role Specific qualifier value Spleen Systemic Lupus Erythematosus Systems Development T cell differentiation T-Cell Receptor T-Lymphocyte Testing Therapeutic Intervention Thymus Gland Tuberculosis bone cytokine genome-wide graft vs host disease helix-loop-helix protein differentiation inhibitor insight interest interleukin-21 killer T cell prevent programs protein function public health relevance receptor research study response thymocyte transcription factor

项目摘要

DESCRIPTION (provided by applicant): Natural killer (NK) T cells are a subset of lymphocytes that play an important role in the response to M. tuberculosis and in preventing autoimmune disease and cancer but their inappropriate activation can lead to diseases such as atherosclerosis, allergy or asthma. NKT cells recognize glycolipid antigen presented on CD1d through their T cell receptor but they also express activating receptors commonly associated with NK cells, and they exist in an primed state allowing them to produce copious amounts of cytokine rapidly after encounter with antigen. NKT cells acquire this effector phenotype as a consequence of their unique mechanism of selection and differentiation in the thymus. However, the range of effector fates that NKT cells can acquire is only beginning to be appreciated and the mechanisms controlling NKT cell effector fate choice is completely unknown. My research is directed at understanding the molecular mechanisms that control development of adaptive and innate lymphocytes with a focus on the E protein basic helix-loop-helix (bHLH) transcription factors and their antagonists the Id proteins. These proteins are critical regulators of lymphocyte development and in the NKT cell lineage we hypothesize that these bHLH proteins control both positive selection of NKT cells and their choice of effector cell fate. In this grant application w propose to determine: 1) the range of NKT cell effector fates controlled by bHLH proteins and 2) the role of E protein dose in selection of the E protein target genes that drive these effector fat choices. Our studies will have a major impact on our understanding of how NKT cells function and how their development and effector states are controlled. In addition, our studies will provide insight into mechanisms to manipulate NKT cell effector fate and thereby alter immune responses at their inception.

描述（由申请人提供）：天然杀伤（NK）T细胞是淋巴细胞的一部分，在对结核分枝杆菌的反应以及预防自身免疫性疾病和癌症方面起着重要作用，但它们的不适当激活可能会导致诸如动脉粥样硬化，升高或哮喘等疾病。 NKT细胞通过其T细胞受体识别在CD1D上呈现的糖脂抗原，但它们也表达了通常与NK细胞相关的激活受体，并且它们存在于启动状态下，从而使它们能够在与抗原相遇后快速产生大量的细胞因子。 NKT细胞由于其在胸腺中选择和分化的独特机制而获得了这种效应表型。但是，NKT细胞可以获取的效应命运范围才被开始得到理解，并且控制NKT细胞效应命运选择的机制是完全未知的。我的研究旨在理解控制自适应和先天淋巴细胞发展的分子机制，重点是E蛋白碱性螺旋 - 环螺旋（BHLH）转录因子及其拮抗剂ID蛋白。这些蛋白质是淋巴细胞的关键调节剂发育和NKT细胞谱系中，我们假设这些BHLH蛋白控制着NKT细胞的阳性选择及其对效应细胞命运的选择。在此赠款应用中，w提出：1）由BHLH蛋白控制的NKT细胞效应命运的范围，以及2）E蛋白剂量在选择E蛋白靶基因的作用，从而驱动这些效应脂肪选择的E蛋白靶基因。我们的研究将对我们对NKT细胞的功能以及其开发和效应状态的控制的理解产生重大影响。此外，我们的研究将提供对操纵NKT细胞效应子命运的机制，从而改变其成立时的免疫反应。