Sympathetic neural control of T cell function

T细胞功能的交感神经控制

基本信息

批准号：
9333814
负责人：
John David FARRAR
金额：
$ 39.3万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
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：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9333814
关键词：
ADRB2 gene Adrenergic Agents Adrenergic beta-Antagonists Affect Agonist Albuterol Alpha Interleukin 2 Receptor Area Autoimmunity Binding Brain Breathing CD8B1 gene Cell physiology Cells Chronic Circadian Rhythms Cytotoxic T-Lymphocytes Data Development Diet Drug usage Effector Cell Epinephrine Event Exercise Family Fright Heart Rate Hormones Human Hydrocortisone IL2RA gene Immune Immune response Immune system Immunity Immunologic Memory Infection Influenza Interleukin-2 Kinetics Lead Learning Ligands Link Lung Lymphoid Tissue Lytic Mediating Memory Metabolic MicroRNAs Modeling Molecular Moods Mus Nervous System control Nervous system structure Neural Pathways Neurons Neurotransmitter Receptor Neurotransmitters Norepinephrine Organ Organism Pathway interactions Peristalsis Pharmaceutical Preparations Phase Physiological Processes Play Psyche structure Role Scientist Signal Transduction Sleep Stimulus Stress Sympathetic Nervous System System T memory cell T-Cell Development T-Cell Receptor T-Lymphocyte Testing Time Tissues Vaccination Vesicular stomatitis Indiana virus Viral Respiratory Tract Infection Virus Diseases Well in self adaptive immunity asthmatic patient atopy base beta-2 Adrenergic Receptors blood pressure regulation constriction cytokine fighting genetic manipulation immune function in vivo insight interest member mind control neuroregulation neurotransmission prevent public health relevance receptor receptor binding response selective expression transcriptome

项目摘要

PROJECT SUMMARY – ABSTRACT This application seeks to understand how the brain, through signals delivered via sympathetic neurons, controls immune function. The sympathetic nervous system controls a variety of cellular and metabolic functions and plays a critical role in the flight or fight response. The adrenergic class of neurotransmitter receptors binds to nor-epinephrine secreted by sympathetic neurons and is a target of various pharmacological agonists and antagonists used in humans. Very little is known about how this pathway interfaces with the immune system. We recently found selective expression of the β2-adrenergic receptor (ADRB2) on human CD8+ memory T cells, and it is also expressed in murine CD8+ T cells. Signaling through this receptor significantly suppressed various effector T cell functions including cytokine secretion and lytic activity. Further, CD8+ CTLs lacking the ADRB fail to generate memory cells following infection with vesicular stomatitis virus. Given the importance of this pathway in regulating multiple physiological processes, we wished to determine the role of the ADRB2 in regulating the major functions of adaptive cytolytic T cells of the immune system. Aim 1 will determine how intrinsic ADRB2 signaling regulates the development and function of both effector and memory CD8+ CTLs in response to intracellular infections. Aim 2 will identify the molecular pathway that drives ADRB2-mediated memory development. Finally, Aim 3 will determine how long-acting β-agonist drugs alter the course of a primary and secondary immune response to flu infection. These studies will inform us on the role of the sympathetic nervous system in regulating cytolytic T cell function and how pharmacological agonists alter those responses.

项目摘要 – 摘要该应用程序旨在了解大脑如何通过交感神经元传递的信号，控制免疫功能。交感神经系统控制多种细胞和代谢。肾上腺素能神经递质在逃跑或战斗反应中发挥着重要作用。受体与交感神经元分泌的去甲肾上腺素结合，是多种药理作用的靶点对于人类中使用的激动剂和拮抗剂知之甚少。我们最近发现β2-肾上腺素受体（ADRB2）在人类身上选择性表达。 CD8+ 记忆 T 细胞，也通过该受体在小鼠 CD8+ T 细胞中表达。显着抑制各种效应 T 细胞功能，包括细胞因子分泌和裂解活性。缺乏 ADRB 的 CD8+ CTL 在感染水泡性口炎病毒后无法生成记忆细胞。鉴于该途径在调节多种生理过程中的重要性，我们希望确定 ADRB2 在调节免疫系统适应性溶细胞 T 细胞的主要功能中的作用。 1 将确定内在的 ADRB2 信号如何调节效应器和记忆 CD8+ CTL 响应细胞内感染，目标 2 将确定驱动的分子途径。最后，目标 3 将确定长效 β 激动剂药物如何改变。这些研究将为我们提供有关流感感染的初级和次级免疫反应的信息。交感神经系统在调节溶细胞性 T 细胞功能中的作用以及药理学激动剂的作用改变这些反应。