Regulation of innate lymphocyte function by Zbtb32

Zbtb32 对先天淋巴细胞功能的调节

基本信息

批准号：
8869820
负责人：
Aimee Melissa Beaulieu
金额：
$ 16.2万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
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：
2016-02-05 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8869820
关键词：
Address Allergic Disease Antiviral Response Autoimmune Diseases Autoimmunity B-Lymphocytes CD4 Positive T Lymphocytes Cell Lineage Cell Proliferation Cell physiology Cells ChIP-seq Co-Immunoprecipitations Common Lymphoid Progenitor Complex Data Dependency Development Diagnostic tests Disease Faculty Family Gene Targeting Goals Helminths Human Hypersensitivity Immune Immune response Immune system Immunity Infection Inflammation Influenza Interleukin 2 Receptor Gamma Investigation K22 Award Knowledge Link Lung Lymphocyte Lymphocyte Function Lymphocyte Subset Lymphoid Cell Malignant Neoplasms Mediator of activation protein Microbe Molecular Mus Natural Killer Cells Organ Pathway interactions Play Population Positioning Attribute Regulation Reporting Research Research Personnel Research Proposals Resources Role Signal Pathway Skin Stem cells Structure of germinal center of lymph node T-Lymphocyte Testing Time Tissues Transcription Repressor/Corepressor Vaccines Viral Virus Virus Diseases ZNF145 gene Zinc Fingers adaptive immunity antiviral immunity career cytokine effective therapy fascinate gene repression human disease in vivo novel novel therapeutics pathogen post-doctoral training programs public health relevance receptor repaired research study response tenure track transcription factor

项目摘要

DESCRIPTION (provided by applicant): The immune system responds to infection with a complex interplay of immune cells and secreted factors aimed at eliminating the intruding pathogen and repairing damaged tissue. Innate lymphocytes, which include NK cells, NKT cells, T cells, and the newly discovered innate lymphoid cells (ILCs), are a fascinating and relatively understudied subset of immune cells that function at the interface of innate and adaptive immune responses. My goal is to establish independent research program focused on understanding the molecular pathways that regulate effector responses by innate lymphocytes during infection. During my postdoctoral training, I discovered a novel signaling pathway involving the transcription factors Zbtb32 and Blimp-1 that critically regulates anti-viral responses by NK cells1. As an independent faculty researcher, I plan to continue my investigation of how Zbtb32 regulates anti-pathogen responses by innate lymphocytes. Specifically, the studies proposed in this K22 application aim to: (1) determine whether Zbtb32 and Blimp-1 physically interact in NK cells and whether Zbtb32 influences the suite of genes targeted by Blimp- 1 for transcriptional repression; and (2) explore whether Zbtb32 regulates anti-viral immune responses by Type 2 ILCs during influenza infection in vivo. Given the remarkable range of diseases regulated by innate lymphocytes, including viral, bacterial, and helminth infections, and allergic and autoimmune diseases, the proposed studies will have important applications in the development of new therapies, vaccines, and diagnostic tests for a wide variety of human illnesses. Moreover, support from this K22 award would provide me with key time and resources to successfully transition into a tenure-track faculty position and to acquire the knowledge and data I will need to launch a productive and sustainable independent research career.

描述（由适用提供）：免疫系统应对免疫细胞的复杂相互作用和旨在消除侵入病原体和修复损坏的组织的分泌因子的感染做出反应。先天淋巴细胞，包括NK细胞，NKT细胞，t细胞和新发现的先天淋巴样细胞（ILC），是一种令人着迷的和相对理解的免疫细胞的子集，可在先天和适应性免疫调查的界面起作用。我的目标是建立独立的研究计划，专注于了解在感染过程中先天淋巴细胞调节效应子反应的分子途径。在博士后训练中，我发现了一种新颖的信号通路涉及转录因子ZBTB32和Blimp-1，该因子严格调节NK细胞的抗病毒反应1。作为一名独立的教师研究员，我计划继续对ZBTB32如何调节先天淋巴细胞的抗病原体反应的投资。具体而言，在此K22应用中提出的研究目的是：（1）确定ZBTB32和Blimp-1是否在NK细胞中物理相互作用以及ZBTB32是否影响Blimp-1靶向转录表达的基因套件；（2）探索ZBTB32是否在体内影响期间按2型ILC调节抗病毒免疫反应。鉴于由先天淋巴细胞调节的疾病范围很大，包括病毒，细菌和头盔感染，以及过敏性和自身免疫性疾病，因此拟议的研究将在开发新疗法，疫苗，疫苗和诊断诊断性的各种人类疾病方面具有重要应用。此外，该K22奖的支持将为我提供关键的时间和资源，以成功地过渡到终身教师职位，并获得我将需要开展富有成效且可持续的独立研究职业的知识和数据。