Biological Rhythms and Immune Function

生物节律和免疫功能

• 批准号: 8468978
• 负责人: BRIAN J PRENDERGAST
• 金额: $ 36.66万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468978
• 关键词: Acute; Affect; Bacterial Infections; Behavior; Biological; Biological Clocks; Biological Rhythm; Brain; Cells; Chronic Disease; Circadian Rhythms; Cognition; Coupling; Diagnostic; Endocrine; Endocrine system; Exhibits; Exposure to; Gene Expression; Goals; Hamsters; Health; Hour; Human; Hypothalamic structure; Immune; Immune system; Immunity; Immunocompetence; Immunocompromised Host; Infection; Inflammation; Inflammatory Response; Investigation; Leukocytes; Light; Lymphocyte; Lymphoid; Malignant Neoplasms; Measures; Mediating; Melatonin; Modeling; Moods; Morbidity - disease rate; Nervous system structure; Neuraxis; Obesity; Output; Peripheral; Personal Satisfaction; Phenotype; Reaction; Research; Role; Seasonal Variations; Siberian Hamster; Signal Transduction; Specific qualifier value; T-Lymphocyte; Thyroid Hormones; Time; Virus Diseases; Work; circadian pacemaker; day length; immune function; innate immune function; insight; novel; public health relevance; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): The immune system and the central nervous system interact in a bidirectional manner. Activity of the central nervous system can direct marked changes in immune function. Likewise, peripheral inflammation is associated with pathological changes in motivational states and behavior, mood and cognition. Circadian and seasonal clocks in the hypothalamus yield high-amplitude rhythms in immune function and afford direct investigation of mechanisms mediating brain-to-immune interactions. Daily and seasonal rhythms in morbidity in response to inflammation are directly relevant to survival of numerous illnesses. Understanding how biological clocks engage changes in the immune system has implications for the treatment and management of chronic diseases (e.g., cancer, obesity) and acute bacterial and viral infections. The overall goal of the proposed research is to identify the mechanisms by which daily (circadian) and seasonal time information is communicated from the brain to the immune system. Siberian hamsters will be used as a model species specifically because they exhibit robust seasonal and circadian rhythms in innate and adaptive immune function which can be readily driven and synchronized by changes in the light-dark cycle. In this species, the amplitude of the seasonal cycle in several measures of immunity encompasses a range that would be clinically diagnostic of an immunocompromised state, yet hamsters exhibit these changes in immunity in the absence of co-morbid illness and in response to little more than a few hours' change in the light-dark cycle. Understanding the mechanisms by which time information drives changes in immune function will identify novel endogenous mechanisms by which the brain affects the immune system. This is a fundamentally-important issue which will inform treatments for seasonally-recurring illnesses in humans, and the causes of robust circadian rhythms in morbidity. These experiments will assess redistribution of blood leukocyte phenotypes, alterations in adaptive T cell-mediated immune function (DTH reactions), and changes in the magnitude of infection-induced innate inflammatory responses in experiments that seek to: (1) identify the cellular mechanisms by which changes in day length and melatonin control immune cell activity, (2) specify the role of thyroid hormone signaling in the genesis of seasonal changes in the immune system, (3) characterize the influence of the hypothalamic circadian pacemaker on daily rhythms in the immune system and on organismal-level immunocompetence, and (4) identify the output mechanisms that mediate coupling between the circadian clock and the immune system. The proximate causes of human seasonal and circadian rhythms in health and immune function remain largely unknown. Together, the work will afford major and novel biological insights into the mechanisms by which the nervous and endocrine systems guide the activity of the immune system.

描述（由申请人提供）：免疫系统和中枢神经系统以双向方式相互作用。中枢神经系统的活性可以指导免疫功能的明显变化。同样，周围炎症与动机状态和行为，情绪和认知的病理变化有关。下丘脑中的昼夜节律和季节钟在免疫功能中产生高振幅节奏，并可以直接研究介导脑之间相互作用的机制。响应炎症的每日和季节性节奏与多种疾病的生存直接相关。了解生物钟如何参与免疫系统的变化对慢性疾病（例如癌症，肥胖症）和急性细菌和病毒感染的治疗和管理具有影响。 拟议研究的总体目标是确定每天（昼夜节律）和季节性信息从大脑传达到免疫系统的机制。西伯利亚仓鼠将被用作模型物种，特别是因为它们在先天和适应性免疫功能中表现出强大的季节性和昼夜节律，可以很容易地通过灯光周期的变化来驱动和同步。在该物种中，季节性周期的几种免疫力幅度包括一个临床诊断的免疫功能低下状态的范围，但是在没有共蛋性疾病的情况下，仓鼠在没有互助疾病的情况下显示出这些免疫力的变化，并且在光明周期中几个小时的变化却几乎没有响应。了解时间信息导致免疫功能变化的机制将确定大脑影响免疫系统的新型内源性机制。这是一个从根本上重要的问题，它将为人类季节性疾病的治疗方法提供依据，以及发病率强大的昼夜节律的原因。 These experiments will assess redistribution of blood leukocyte phenotypes, alterations in adaptive T cell-mediated immune function (DTH reactions), and changes in the magnitude of infection-induced innate inflammatory responses in experiments that seek to: (1) identify the cellular mechanisms by which changes in day length and melatonin control immune cell activity, (2) specify the role of thyroid hormone signaling in the genesis在免疫系统的季节性变化中，（3）表征下丘脑昼夜节律起搏器对免疫系统中每日节奏和有机体免疫能力的影响，（4）确定介导昼夜节律时钟和免疫系统之间偶联的输出机制。人类季节性和昼夜节律在健康和免疫功能方面的最直接原因仍然未知。这项工作将提供有关神经和内分泌系统指导免疫系统活性的机制的主要和新颖的生物学见解。