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

• 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
• 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

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）：自然杀伤（NK） T细胞是淋巴细胞的一个子集，在对结核分枝杆菌的反应和预防自身免疫性疾病和癌症中起重要作用，但它们的不适当激活可导致动脉粥样硬化、过敏或哮喘等疾病。NKT细胞通过其T细胞受体识别CD1d上的糖脂抗原，但它们也表达通常与NK细胞相关的激活受体，它们处于启动状态，使它们在遇到抗原后迅速产生大量的细胞因子。NKT细胞获得这种效应表型是由于其在胸腺中独特的选择和分化机制。然而，NKT细胞可以获得的效应命运的范围才刚刚开始被认识，控制NKT细胞效应命运选择的机制是完全未知的。我的研究方向是了解控制适应性和先天淋巴细胞发育的分子机制，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。这些蛋白是淋巴细胞的重要调节因子