Characterization of stimulatory and inhibitory immunoregulatory receptors in bony fish

硬骨鱼刺激性和抑制性免疫调节受体的表征

• 批准号: 341209-2012
• 负责人: Stafford, James
• 金额: $ 2.48万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=595347
• 关键词: Characterization; stimulatory; inhibitory; immunoregulatory; receptors

The immune system is composed of a vast array of proteins and cells, which together play a pivotal role in the detection and elimination of invading pathogens. Compromised or dysfunctional immunity can cause dissemination of bacterial and viral diseases and/or potentially life-threatening hypersensitivity reactions and debilitating autoimmune conditions such as lupus and rheumatoid arthritis. Therefore, precise control and coordination of immune responses is essential for the rapid detection and elimination of pathogens while limiting damage to surrounding tissues. The regulation of cellular immune responses is in part mediated by several immune proteins expressed on cell surfaces that translate environmental cues into functional responses via complex intracellular signaling cascades. Termed immunoregulatory receptors, these proteins are involved in all aspects of cellular immunity and understanding how they influence immune responses provides important information for the design of immunotherapeutic strategies. This knowledge has made significant contributions for combating infections and abrogating allergic responses and autoimmune diseases. Although much is known about immunoregulatory receptor-mediated control of the human immune system, investigations using non-mammalian model systems have recently provided novel insights into conserved mechanisms of immune cell control. This comparative approach for understanding vertebrate immunity has made significant contributions to the design of novel therapeutic strategies for improving human health. Our work focuses on understanding how immunoregulatory receptors control immunity in bony fishes, which allows us to uncover both conserved and unique aspects of immune system control and coordination in two vertebrate species that diverged more than 400 million years ago. Based on the contributions that these investigations have already provided, we anticipate that our studies will continue to provide important information required for an in depth understanding of conserved strategies of immune system protection mechanisms in vertebrates that may lead to improved methods for augmenting or abrogating specific immune responses.

免疫系统由大量的蛋白质和细胞组成，它们共同在检测和消除入侵病原体方面发挥着关键作用。免疫受损或功能障碍可导致细菌和病毒疾病的传播和/或潜在威胁生命的超敏反应，以及削弱自身免疫状况，如狼疮和类风湿性关节炎。因此，精确控制和协调免疫反应对于快速检测和消除病原体，同时限制对周围组织的损害是至关重要的。细胞免疫反应的调节在一定程度上是由细胞表面表达的几种免疫蛋白介导的，这些免疫蛋白通过复杂的细胞内信号级联将环境信号转换为功能反应。这些蛋白被称为免疫调节受体，参与细胞免疫的各个方面，了解它们如何影响免疫反应为设计免疫治疗策略提供了重要信息。这一知识为抗击感染、消除过敏反应和自身免疫性疾病做出了重大贡献。虽然对免疫调节受体介导的人类免疫系统控制已知很多，但使用非哺乳动物模型系统的研究最近为免疫细胞控制的保守机制提供了新的见解。这种理解脊椎动物免疫的比较方法对设计新的治疗策略以改善人类健康做出了重大贡献。我们的工作重点是了解免疫调节受体如何控制多骨鱼类的免疫，这使我们能够揭示两个在4亿多年前分裂的脊椎动物物种的免疫系统控制和协调的保守和独特方面。基于这些研究已经提供的贡献，我们预计我们的研究将继续提供深入了解脊椎动物免疫系统保护机制保守策略所需的重要信息，这可能导致增强或取消特定免疫反应的改进方法。