The biological relevance of adenosine deamination in immune activation

腺苷脱氨基作用在免疫激活中的生物学相关性

• 批准号: 7238533
• 负责人: YAN SHI
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF CALGARY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7238533
• 关键词: Address; Adenosine; Adjuvant; Adult; Anti-Inflammatory Agents; Anti-inflammatory; Antibody Formation; Antiviral Response; Apoptosis; Autoimmune Diseases; Biological; Biological Assay; Categories; Cells; Cellular Infiltration; Chimera organism; Condition; Cytotoxic T-Lymphocytes; Data; Deamination; Dendritic Cells; Dendritic cell activation; Depth; Development; Disease; Enzymes; Event; Foundations; Future; Host Defense; Immune; Immune response; Immune system; In Vitro; Individual; Infection; Inflammation; Inflammatory Response; Injury; Intervention; Knockout Mice; Lead; Nucleosides; Outcome Study; Phenotype; Play; Production; Purinergic P1 Receptors; Rate; Reaction; Regulation; Research; Role; Series; Signal Transduction; Standards of Weights and Measures; Stress; T-Cell Activation; Testing; Thinking; Tissues; Urination; Work; adenosine deaminase; cancer immunotherapy; concept; cytokine; immune function; in vitro Assay; in vivo; microbial; reconstitution; vaccine development

DESCRIPTION (provided by applicant): Adenosine is a potent suppressive agent that protects the host from excessive tissue injury associated with strong inflammation. In tissue stress, including infections, adenosine production is elevated. The higher levels of adenosine signal through adenosine receptors to exert strong anti-inflammatory effects, and thus protect host cells. Under in vitro settings, this suppressive effect is evident in immune cells as well. Adenosine, therefore, has been thought as playing a role of "calming" the immune system in disease conditions. This popular notion, however, is in contrast with another basic observation that the immune system is most activated precisely under the same circumstances. In our preliminary in vitro assays we discovered that dendritic cells, the initiator of immune reactions, used adenosine deaminase to rapidly remove adenosine from their surroundings. We hypothesize that this enzymatic activity may isolate dendritic cells from the suppression of adenosine, rendering them fully functional in infections. We propose here a set of common and highly optimized immunological assays to test the validity of this hypothesis in vivo. The outcome of this study will pave the way for future explorations on the topic. This study deals with a new concept in immune regulation, and will have impact on vaccine development, autoimmune disease intervention and cancer immunotherapy.

描述（由申请人提供）：腺苷是一种有效的抑制剂，可保护宿主免受与强烈炎症相关的过度组织损伤。在组织应激中，包括感染，腺苷的产生升高。较高水平的腺苷信号通过腺苷受体发挥强大的抗炎作用，从而保护宿主细胞。在体外环境下，这种抑制作用在免疫细胞中也很明显。因此，腺苷被认为在疾病条件下起着“平静”免疫系统的作用。然而，这个流行的观点与另一个基本观察相反，即免疫系统在相同的情况下被激活得最多。在我们初步的体外试验中，我们发现树突状细胞，免疫反应的启动者，使用腺苷脱氨酶快速从周围环境中去除腺苷。我们假设这种酶活性可以将树突状细胞从腺苷的抑制中分离出来，使它们在感染中完全发挥作用。我们在这里提出了一套常见的和高度优化的免疫学检测，以测试这一假设在体内的有效性。这项研究的结果将为今后关于这一专题的探讨铺平道路。该研究为免疫调节提供了新的概念，并将对疫苗开发、自身免疫性疾病干预和癌症免疫治疗产生影响。