Sympathetic neural control of T cell function

T细胞功能的交感神经控制

• 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
• 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

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 这个应用程序试图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 在飞行或战斗反应中起着关键作用。肾上腺素能神经递质 受体与交感神经元分泌的去甲肾上腺素结合， 用于人类的激动剂和拮抗剂。关于这一途径如何与 免疫系统我们最近发现β2-肾上腺素能受体（β2-adrenergic receptor，ADRB 2）在人胚肾细胞中有选择性表达， CD 8+记忆T细胞，并且其也在鼠CD 8 + T细胞中表达。通过这个受体传递信号 显著抑制各种效应T细胞功能，包括细胞因子分泌和裂解活性。此外，本发明还 缺乏ADRB的CD 8 + CTL在感染水泡性口炎病毒后不能产生记忆细胞。 考虑到该通路在调节多种生理过程中的重要性，我们希望确定 ADRB 2在调节免疫系统的适应性溶细胞性T细胞的主要功能中的作用。目的 1将确定内源性ADRB 2信号传导如何调节效应子和受体的发育和功能。 记忆CD 8 + CTL应答细胞内感染。目标2将确定驱动基因的分子途径， ADRB 2介导的记忆发育。最后，目标3将确定长效β受体激动剂药物如何改变 对流感感染的初级和次级免疫反应的过程。这些研究将告诉我们， 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 改变这些反应。