Molecular regulation of T cell activation signals by TRAF3

TRAF3 对 T 细胞激活信号的分子调节

基本信息

批准号：
9075045
负责人：
GAIL A. BISHOP
金额：
$ 37.97万
依托单位：
UNIVERSITY OF IOWA
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：
2016-02-01 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9075045
关键词：
Address Antigen Receptors Antigens Autoimmune Process B-Lymphocytes Behavior Biological Response Modifiers CD28 gene CD3 Antigens Cell Line Cells Cellular biology Communicable Diseases Complex Cytokine Receptors Cytoplasm Cytoplasmic Tail Data Epithelial Family Fibroblasts Health IFNAR1 gene Immune Immune system Immunology Inflammatory Interferon Receptor Knowledge Lead Ligation Lymphocyte Biology Mediating Membrane Mission Mitogen-Activated Protein Kinases Molecular Myelogenous Myeloid Cells Nature Organism Outcome PTPN22 gene Pathway interactions Phosphoric Monoester Hydrolases Phosphotransferases Play Process Proteins Public Health Publishing Receptor Signaling Regulation Research Role Signal Pathway Signal Transduction T-Cell Activation T-Cell Receptor T-Lymphocyte TNF Receptor-Associated Factors TNF receptor-associated factor 3 TNFRSF5 gene Therapeutic Tumor Necrosis Factor Receptor United States National Institutes of Health adapter protein cell type cytokine improved inhibitor/antagonist member novel overexpression protein protein interaction public health relevance receptor tumor type I interferon receptor

项目摘要

DESCRIPTION (provided by applicant): The number and variety of immune cell receptors and signaling pathways shown to be regulated by the tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) has steadily grown in recent years. TRAF3, initially identified through its association with the CD40 receptor, has emerged as an especially versatile regulator of immune processes. Previously, TRAF3 was studied primarily in B lymphocytes, myeloid cells, and non-immune cells. However, recent studies reveal that TRAF3 also plays several important and distinct roles in regulation of T lymphocyte biology, although how this occurs is only starting to be unraveled. The proposed project focuses upon this knowledge gap, and aims to fulfill a critical need to understand how TRAF3 regulates T cell activation. This question will be pursued in three Specific Aims, to uncover: 1) The role of TRAF3 in facilitating TCR signaling. 2) The role of TRAF3-CD28 interactions in regulation of T cell signaling and 3) The role of TRAF3 in restraining signaling to T cells by the type 1 interferon receptor (IFNAR). The expected outcomes of this project are important new knowledge that will revise fundamental understanding of T cell signaling, providing novel basic immunology knowledge that will in turn inform potential therapeutic applications that seek to manipulate the process of T cell activation.

描述（由适用提供）：近年来，被肿瘤坏死因子受体（TNFR）相关因子（TRAFS）所调节的免疫细胞受体和信号通路的数量和种类逐渐增长。 TRAF3最初通过其与CD40受体的关联确定，已成为免疫过程的特殊调节剂。以前，TRAF3在B淋巴细胞，髓样细胞和非免疫细胞中是研究。然而，最近的研究表明，TRAF3在调节T淋巴细胞生物学中也起着几种重要和不同作用被解开。拟议的项目着重于这一知识差距，并旨在满足批判性需求，以了解TRAF3如何调节T细胞激活。这个问题将在三个特定目标中提出，以揭示：1）TRAF3在促进TCR信号传导中的作用。 2）角色 TRAF3-CD28在调节T细胞信号传导中的相互作用和3）Traf3在将信号传导通过1型干扰素受体（IFNAR）限制为T细胞中的作用。该项目的预期结果是重要的新知识，它将修改对T细胞信号传导的基本理解，从而提供新颖的基本免疫学知识，进而为潜在的治疗应用提供了旨在操纵T细胞激活过程的潜在治疗应用。