Spleen glia in autonomic regulation of immunity

脾胶质细胞在免疫自主调节中的作用

基本信息

批准号：
9317544
负责人：
MARION S BUCKWALTER
金额：
$ 20.45万
依托单位：
STANFORD UNIVERSITY
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：
2016-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9317544
关键词：
Adrenal Cortex Hormones Adrenergic Agents Adrenergic Receptor Anatomy Antibodies Antigen-Presenting Cells Antigens Appearance Area Arthritis Asthma Astrocytes Autoimmune Diseases B-Lymphocytes Bioinformatics Brain Bromodeoxyuridine Cells Communicable Diseases Communication Cues Cytokine Receptors Data Disease susceptibility Epinephrine Female Funding Gene Expression Genes Glial Fibrillary Acidic Protein Gut associated lymphoid tissue Homeostasis Immune Immune response Immune system Immunity Immunologic Markers Immunoprecipitation Immunosuppressive Agents Location Lung Lymphocyte Lymphoid Malpighian corpuscles Mediating Messenger RNA Middle Cerebral Artery Infarction Morphology Multiple Sclerosis Mus Nerve Nerve Endings Neuroglia Neuroimmune Neurons Neurotransmitters Non-Visceral Norepinephrine Organ PTPRC gene Participant Pathway Analysis Peripheral Phenotype Physiological Play Positioning Attribute Production Publishing Regulation Research Design Rest Ribosomes Role Schwann Cells Scientific Inquiry Severities Signal Pathway Signal Transduction Site Spleen Stress Stroke Structure Structure of germinal center of lymph node Sympathetic Nervous System T-Lymphocyte Testing Time Transgenic Mice Translating Tyrosine 3-Monooxygenase Vascular blood supply adaptive immune response adaptive immunity candidate marker chemokine cytokine experimental study high risk immune depression immune function immunoregulation interest lymph nodes male nerve supply neuroinflammation novel marker receptor response sham surgery tool transcriptome transcriptome sequencing

Adrenal Cortex Hormones Adrenergic Agents Adrenergic Receptor Anatomy Antibodies Antigen-Presenting Cells Antigens Appearance Area Arthritis Asthma Astrocytes Autoimmune Diseases B-Lymphocytes Bioinformatics Brain Bromodeoxyuridine Cells Communicable Diseases Communication Cues Cytokine Receptors Data Disease susceptibility Epinephrine Female Funding Gene Expression Genes Glial Fibrillary Acidic Protein Gut associated lymphoid tissue Homeostasis Immune Immune response Immune system Immunity Immunologic Markers Immunoprecipitation Immunosuppressive Agents Location Lung Lymphocyte Lymphoid Malpighian corpuscles Mediating Messenger RNA Middle Cerebral Artery Infarction Morphology Multiple Sclerosis Mus Nerve Nerve Endings Neuroglia Neuroimmune Neurons Neurotransmitters Non-Visceral Norepinephrine Organ PTPRC gene Participant Pathway Analysis Peripheral Phenotype Physiological Play Positioning Attribute Production Publishing Regulation Research Design Rest Ribosomes Role Schwann Cells Scientific Inquiry Severities Signal Pathway Signal Transduction Site Spleen Stress Stroke Structure Structure of germinal center of lymph node Sympathetic Nervous System T-Lymphocyte Testing Time Transgenic Mice Translating Tyrosine 3-Monooxygenase Vascular blood supply adaptive immune response adaptive immunity candidate marker chemokine cytokine experimental study high risk immune depression immune function immunoregulation interest lymph nodes male nerve supply neuroinflammation novel marker receptor response sham surgery tool transcriptome transcriptome sequencing

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项目摘要

Project Summary. Stress strongly influences the immune system, particularly antigen-specific adaptive immune responses, via sympathetic outflow and activation of adrenergic receptors. However, although there are consistent findings that the sympathetic neurotransmitters epinephrine and norepinephrine regulate antigen presenting cells and T and B lymphocytes via adrenergic receptors, the results are context dependent–either activation or suppression of antigen-dependent responses is observed. Importantly, the cues that mediate these opposing effects are not well understood. We propose here to generate tools to understand whether spleen glia play an unrecognized role in regulating these context-dependent effects of sympathetic outflow on adaptive immunity. Sympathetic terminals carrying adrenergic neurotransmitters enter the spleen around the arterial blood supply and innervate the white pulp, where antigen-specific T and B lymphocyte responses are continually developing. So glia accompanying the sympathetic nerves are optimally positioned to influence stress effects on antigen-dependent adaptive immune responses. The barrier to testing this is, however, that spleen glia have not previously been described. We are therefore requesting R21 funding to describe their anatomy and translatome (translating mRNAs), and to determine if they change their expression of immune genes during the extreme physiological stress of a large stroke. At the conclusion of these experiments, we will have generated tools to study not only spleen glia, but also other peripheral glia, and also have established whether spleen glia are important participants in sympathetically-mediated effects on immune responses. These studies are appropriate for R21 funding as they are high-risk initial studies in a new scientific area, the study of the functions of spleen glia.

项目摘要。压力强烈影响免疫系统，尤其是抗原特异性适应性免疫回报。交感神经出口和肾上腺素受体的激活。但是，尽管有一致的发现交感神经递质肾上腺素和去甲肾上腺素调节抗原呈递细胞和T 和B淋巴细胞通过肾上腺素接收器，结果取决于上下文 - 激活或观察到抗原依赖性反应的抑制。重要的是，调解这些对立的提示效果不太了解。我们在这里建议生成工具，以了解脾胶质性是否在玩在控制同情出口对适应性免疫组织化学的这些依赖上下文依赖性作用方面，无法识别的作用。携带肾上腺神经递质的交感神经终端进入动脉血液供应周围的脾脏并支配白色果肉，其中抗原特异性T和B淋巴细胞反应是连续的发展。因此，神经胶质采用交感神经系统的最佳位置以影响压力效应关于抗原依赖性的适应性免疫反应。然而，测试这一点的障碍是脾粒神经胶质以前尚未描述。因此，我们要求R21资金来描述其解剖结构和翻译（翻译mRNA），并确定它们是否改变了其在此期间的免疫基因的表达大风的极端身体压力。在这些实验的结论中，我们将生成不仅研究脾胶质神经胶质的工具，还可以研究其他外周神经胶质，并且还确定了脾脏胶质是对对称介导的免疫反应影响的重要参与者。这些研究是适用于R21资金，因为它们是在新科学领域的高风险初始研究， Shelen Glia的功能。