Regulation of Immune Responses by interleukin-23

IL-23 对免疫反应的调节

• 批准号: 7485883
• 负责人: Amy Nicole Sieve
• 金额: $ 5.15万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485883
• 关键词: Antigen-Presenting Cells; Autoimmune Process; Binding; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Differentiation process; Cell Proliferation; Cells; Condition; Data; Disease; Family; Generations; Immune response; Immunity; Infection; Inflammatory; Interferon Type II; Interferons; Interleukin-12; Interleukin-17; Investigation; Knowledge; Lipopolysaccharides; Listeria monocytogenes; Mediating; Microbe; Mus; Mycoplasma pulmonis; Play; Production; Receptor Activation; Regulation; Reporting; Role; Signal Pathway; Signal Transduction; T-Lymphocyte; T-Lymphocyte Subsets; cell type; cytokine; design; disorder control; in vivo; information gathering; interleukin-12 receptor; interleukin-23; novel; pathogen; receptor; research study; response

DESCRIPTION (provided by applicant): Interleukin- 23 (IL-23), which belongs to the IL-12 family of cytokines, has previously been described as having either redundant functions with IL-12 or promoting the differentiation of a novel CD4 T cell subset that produces IL-17. However, our data is the first to indicate that IL-23 can also negatively regulate the secretion of IFN-gamma that is induced by IL-12. Furthermore, we have also shown that IL-23 is involved in promoting IL-17 secreting CD8T cells. Our results have led us to hypothesize that IL-23 plays a novel and important role in CD8 T cell immunity against pathogens by antagonizing IL-12 induced effector functions and promoting the secretion of IL-17. In specific Aim I, we will determine which CD8 T cell effector functions are regulated by IL-23 and whether or not IL-23 plays a role in regulating IFN-gamma production in response to infections. Specific Aim II will identify the mechanisms and signaling pathways involved in IL-23 mediated regulation of IL-12 induced effector functions. Finally, specific Aim III will determine the role of IL- 23 in promoting the secretion of IL-17 from CD8 T cells. The information gathered from these specific aims will increase our knowledge of how IL-23 can regulate early immune responses against pathogens, by decreasing IFN-gamma production and other CD8 T cell effector functions. These studies will also delineate how IL-23 can impact the generation of adaptive immune responses by promoting IL-17 secreting CD8 T cell responses. The results of the experiments outlined within this proposal will further our knowledge of the role of cytokines, particularly IL-23, in immune responses to infectious pathogens. Understanding immune responses to disease causing microbes will enable us to more efficiently control these diseases.

描述（由申请人提供）：属于IL-12细胞因子家族的白介素23（IL-23）先前被描述为具有IL-12的冗余功能或促进产生IL-17的新型CD4 T细胞子集的分化。但是，我们的数据是第一个表明IL-23还可以负调节IL-12诱导的IFN-GAMMA的分泌。此外，我们还表明IL-23参与促进IL-17分泌CD8T细胞。我们的结果使我们假设IL-23通过拮抗IL-12诱导的效应子功能并促进IL-17的分泌在CD8 T细胞免疫中起新颖而重要的作用。在特定目标I中，我们将确定哪些CD8 T细胞效应子功能受IL-23的调节，以及IL-23是否在调节感染的IFN-GAMMA产生中起作用。具体目标II将确定IL-23介导的IL-12诱导效应函数调节中涉及的机制和信号通路。最后，特定的目标III将确定IL-23在促进CD8 T细胞中IL-17分泌中的作用。从这些特定目标中收集的信息将通过减少IFN-GAMMA产生和其他CD8 T细胞效应子功能来调节IL-23如何调节病原体的早期免疫反应的了解。这些研究还将描述IL-23如何通过促进IL-17分泌CD8 T细胞反应来影响适应性免疫反应的产生。本提案中概述的实验结果将进一步了解我们对细胞因子（尤其是IL-23）在对感染性病原体免疫反应中的作用的了解。了解引起微生物的疾病的免疫反应将使我们能够更有效地控制这些疾病。