PLASTICITY OF NON HUMAN PRIMATE TH17 CELL DIFFERENTIATION IN VITRO

非人灵长类 TH17 细胞体外分化的可塑性

• 批准号: 8357347
• 负责人: Reen Wu
• 金额: $ 5.04万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357347
• 关键词: Adoptive Transfer; Animals; Asthma; Autoimmune Diseases; CD4 Positive T Lymphocytes; California; Cell Differentiation process; Cell Lineage; Cell physiology; Cells; Disease; Funding; Grant; Helper-Inducer T-Lymphocyte; Host Defense; Human Development; In Vitro; Inflammatory; Interleukin-17; Interleukins; Knowledge; Lung diseases; Mediator of activation protein; Modeling; Monkeys; Mucosal Immunity; National Center for Research Resources; National Institute of Environmental Health Sciences; Nature; Pathogenesis; Pilot Projects; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Role; Source; Stem cells; System; Testing; Umbilical Cord Blood; United States National Institutes of Health; base; cost; cytokine; immunoregulation; insight; lung injury; nonhuman primate; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. For various lung diseases, elevated Th17 cells and their secretory products, IL-17A, IL-17F are also noticed. However, the nature of the presence and the function related to IL-17 and Th17 cells remain unclear. For non-human primate, there is a lack of information on the functional roles of Th17 cells and their secretory products in various diseases and inflammatory conditions. Since non-human primate monkey is the closest animal to human, the development of Th17 cell lineage in vitro must be carried out in order to apply the new knowledge into various diseases. For Respiratory Disease Unit at CNRPC, there is an unique opportunity to utilize the adoptive transfer approach to characterize the functions of Th17 cells and their secretory products in the ongoing lung injury and asthma model, supported by NIEHS for past 30 years. The current hypothesis in the pilot project application is that the plasticity of Th17 cell lineage and function is regulated by various cytokines and mediators present in the mucosal immunity. To test this hypothesis, we will develop an in vitro system for non-human primate Th17 cell differentiation from the progenitor cells present in umbilical cord blood and to study the responses of this cell lineage to various cytokines and mediators. We believe this is the first of such a study for non-human primate Th17 cell lineage. Two specific aims are proposed. Aim 1 is to establish an in vitro culture system where non-human primate T na¿ve cells can differentiate into Th17 cell lineage. The second aim is to examine the plasticity of Th17 cell differentiation in response to various cytokines in vitro. Information obtained from these studies will serve as the basis of adoptive transfer experiments to exam the role of Th17 cells in lung diseases.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 选择性产生白细胞介素（IL）-17的辅助性T细胞新谱系的发现为免疫调节，宿主防御和自身免疫性疾病的发病机制提供了令人兴奋的新见解。 对于各种肺部疾病，也注意到Th 17细胞及其分泌产物IL-17 A、IL-17 F的升高。 然而，与IL-17和Th 17细胞相关的存在和功能的性质仍不清楚。 对于非人灵长类动物，缺乏关于Th 17细胞及其分泌产物在各种疾病和炎症状况中的功能作用的信息。由于非人灵长类猴是最接近人类的动物，因此必须进行Th 17细胞谱系的体外开发，以便将新知识应用于各种疾病。 对于CNRPC的呼吸系统疾病部门，有一个独特的机会利用过继转移方法来表征Th 17细胞及其分泌产物在持续肺损伤和哮喘模型中的功能，过去30年来一直得到NIEHS的支持。 目前在试点项目应用中的假设是，Th 17细胞谱系和功能的可塑性受到存在于粘膜免疫中的各种细胞因子和介质的调节。 为了验证这一假设，我们将开发一种体外系统，用于从脐带血中存在的祖细胞分化非人灵长类Th 17细胞，并研究该细胞谱系对各种细胞因子和介质的反应。 我们相信这是首次对非人灵长类Th 17细胞谱系进行此类研究。 提出了两个具体目标。 目的1是建立非人灵长类T细胞可分化为Th 17细胞谱系的体外培养体系。 第二个目的是研究Th 17细胞在体外对各种细胞因子的分化的可塑性。 从这些研究中获得的信息将作为过继转移实验的基础，以检查Th 17细胞在肺部疾病中的作用。