Class I MHC & neuroplasticity - a novel role for a classical immune molecule

I类MHC

• 批准号: RGPIN-2018-06834
• 负责人: Foster, Jane
• 金额: $ 4.66万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763685
• 关键词: Class; MHC; neuroplasticity; novel; role

Inflammation is the body's response to acute or chronic challenge. Infection and injury lead to activation of the innate and/or adaptive arms of the immune system. Hallmarks of inflammation (redness, heat, swelling, pain) were first described more than 2000 years ago by the Roman medical writer Cornelius Celcus (1 AD) and the added feature of loss of function was added in the 19th century. Inflammation is a common feature of disease but is also a necessary component of our body's normal homeostasis. Interestingly, immune signaling of the innate and adaptive immune system is just as important to maintaining good health as it is to disease. In the past few decades, the importance of immune-brain communication to brain health has moved to the forefront of neuroscience and psychiatry. Research efforts have established a role for immune molecules and related signaling systems in normal brain development, neuronal excitability, neurotransmission, neuroplasticity, and behaviour. Evidence shows that molecules originally thought to be unique to the immune system are present and functional in the brain. In fact, the brain and immune system share many molecules including neurotransmitters and their receptors, cytokines and chemokines and their receptors, integrins, and cell adhesion molecules to name a few. The discovery that immune molecules may have non-immune roles in the brain changes the way that we may think about the immune system and has stimulated new research directions aimed at identifying novel roles for immune molecules in normal brain function.Class I MHC is a classical immune molecule with an established role in adaptive immunity. Despite the large body of knowledge on class I MHC immune function, the exact nature and range of its functional possibilities in brain has not been extensively analyzed. Since its presence in neurons was revealed, direct evidence has been provided for its role in normal neuronal development and synaptic plasticity in adult neurons. Work by myself and others demonstrated that its expression profile is dynamic and it acts to some degree as a cellular indicator of stress specifically, its expression is increased in specific neuronal populations dictated by the nature of the stimulus. Our body of work has described changes in class I MHC mRNA expression in neurons in response to both immune and non-immune challenges. Work by others has also demonstrated the functional importance of class I MHC to plasticity in adult hippocampal neurons. Together this evidence suggests that class I MHC neuronal signalling may be important to neuronal viability and function. Importantly, through our NSERC-funded research program, we are learning more about how this immune molecule has dual roles in health and disease. Knowledge gained by this work will provide novel ideas about these roles and encourage more consideration of body-brain interactions in mental wellness and general brain health.

炎症是身体对急性或慢性挑战的反应。感染和损伤导致免疫系统的先天和/或适应性臂的激活。炎症的特征（发红、发热、肿胀、疼痛）最早是在2000多年前由罗马医学作家Cornelius Celcus（公元1年）描述的，功能丧失的特征是在世纪增加的。炎症是疾病的常见特征，但也是我们身体正常稳态的必要组成部分。有趣的是，先天和适应性免疫系统的免疫信号对于维持健康和疾病同样重要。在过去的几十年里，免疫-大脑通信对大脑健康的重要性已经转移到神经科学和精神病学的前沿。研究工作已经确立了免疫分子和相关信号系统在正常大脑发育、神经元兴奋性、神经传递、神经可塑性和行为中的作用。有证据表明，最初被认为是免疫系统特有的分子在大脑中存在并发挥作用。事实上，大脑和免疫系统共享许多分子，包括神经递质及其受体、细胞因子和趋化因子及其受体、整联蛋白和细胞粘附分子，仅举几例。免疫分子在大脑中可能具有非免疫作用的发现改变了我们对免疫系统的认识，并激发了新的研究方向，旨在确定免疫分子在正常大脑功能中的新作用。I类MHC是一种经典的免疫分子，在获得性免疫中具有既定的作用。尽管关于I类MHC免疫功能的大量知识，但其在脑中的功能可能性的确切性质和范围尚未被广泛分析。自从它在神经元中的存在被发现以来，已经为它在正常神经元发育和成年神经元突触可塑性中的作用提供了直接证据。我和其他人的工作表明，它的表达谱是动态的，它在某种程度上作为应激的细胞指标，特别是，它的表达在特定的神经元群体中增加，这取决于刺激的性质。我们的工作描述了I类MHC mRNA在神经元中表达的变化，以响应免疫和非免疫的挑战。其他人的工作也证明了I类MHC对成年海马神经元可塑性的功能重要性。总之，这些证据表明，I类MHC神经元信号可能是重要的神经元的活力和功能。重要的是，通过我们的NSERC资助的研究计划，我们正在更多地了解这种免疫分子如何在健康和疾病中发挥双重作用。通过这项工作获得的知识将为这些角色提供新的想法，并鼓励更多地考虑心理健康和一般大脑健康中的身体-大脑相互作用。