Investigating Helios as a regulator of natural killer cell effector maturation

研究 Helios 作为自然杀伤细胞效应成熟的调节剂

基本信息

批准号：
10608673
负责人：
BARBARA L. KEE
金额：
$ 19.76万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-21 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10608673
关键词：
Acute Myelocytic Leukemia Bacteria Biological Assay Biological Models CD8-Positive T-Lymphocytes Cell Count Cell Differentiation process Cell Maturation Cell physiology Cells Cellular biology Chronic Data Defect Dendritic Cells Development Disease Effector Cell Engineering Family Flow Cytometry Foundations Future Generations Genes Goals Grant Half-Life ITGAM gene Immune response Immunotherapeutic agent In Vitro Inflammatory Interferon Type II Interleukin-15 Laboratories Lymphoid Cell Maintenance Malignant - descriptor Murid herpesvirus 1 Mus Mutate Natural Killer Cells Neoplasm Metastasis Phenotype Play Receptor Cell Regulatory T-Lymphocyte Research Role Testing Therapeutic Therapeutic Intervention Undifferentiated Viral Virus Wild Type Mouse adaptive immune response anti-cancer chemokine chimeric antigen receptor crosslink cytokine cytotoxic experimental study functional loss graft vs leukemia effect in vivo in vivo Model leukemia leukemic stem cell melanoma member neoplastic cell pathogen premature prevent programs receptor receptor expression receptor function recruit response self-renewal stem cell self renewal transcription factor transcription regulatory network transgene expression tumor

项目摘要

Project Summary NK cells play essential roles in the immune response to intracellular pathogens, including viruses and bacteria, and form an important defense against malignant transformation and metastasis. In this R21 application, we propose experiments to test the hypotheses that the transcription factor Helios is a central regulator of undifferentiated NK cells, supporting their self- rewak and limiting effector maturation. We present evidence that Helios is expressed in the most undifferentiated of mature NK cells and up-regulated in Ets1-deficient NK cells, which fail to mature appropriately and have multiple defects in NK cell receptor expression and function. We will create mice lacking Helios, or Ets1 and Helios, in NK cells to determine whether these cells show premature effector maturation and altered response to cytokines, tumor cells (melanoma) or virus (mouse cytomegalovirus). Our studies will provide a foundation for understand the mechanisms underlying NK cell self-renewal effector maturation.

项目概要 NK 细胞在针对细胞内病原体的免疫反应中发挥重要作用，包括病毒和细菌，并形成防止恶性转化和的重要防御转移。在此 R21 应用中，我们提出实验来测试以下假设：转录因子 Helios 是未分化 NK 细胞的中央调节因子，支持其自我重新唤醒并限制效应器成熟。我们提供的证据表明 Helios 表达于大多数未分化的成熟 NK 细胞，在 Ets1 缺陷的 NK 细胞中表达上调，从而失败正常成熟，NK 细胞受体表达和功能存在多种缺陷。我们将创建 NK 细胞中缺乏 Helios 或 Ets1 和 Helios 的小鼠，以确定这些细胞表现出过早的效应成熟和对细胞因子、肿瘤细胞的反应改变（黑色素瘤）或病毒（小鼠巨细胞病毒）。我们的研究将为了解 NK 细胞自我更新效应器成熟的机制。