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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 一种新的辅助T细胞谱系的发现选择性地产生白介素17，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。在各种肺部疾病中，也可见Th17细胞及其分泌产物IL-17A、IL-17F升高。然而，与IL-17和Th17细胞相关的存在的性质和功能仍不清楚。对于非人类灵长类动物，关于Th17细胞及其分泌产物在各种疾病和炎症条件下的功能作用的信息缺乏。由于非人灵长类猴子是最接近人类的动物，为了将新知识应用于各种疾病，必须进行Th17细胞系的体外培养。对于CNRPC的呼吸科，有一个独特的机会，可以利用采用的转移方法来表征Th17细胞及其分泌产物在NIEHS过去30年支持的持续肺损伤和哮喘模型中的功能。目前在试点项目应用中的假设是，Th17细胞谱系和功能的可塑性受到粘膜免疫中存在的各种细胞因子和介质的调节。为了验证这一假设，我们将开发一个从脐带血中存在的祖细胞分化为非人类灵长类Th17细胞的体外系统，并研究该细胞系对各种细胞因子和介质的反应。我们相信这是第一次对非人类灵长类Th17细胞谱系进行这样的研究。提出了两个具体目标。目的1建立非人类灵长类T细胞向Th17细胞分化的体外培养体系。第二个目的是在体外检测Th17细胞分化对各种细胞因子的反应的可塑性。从这些研究中获得的信息将作为过继转移实验的基础，以检验Th17细胞在肺部疾病中的作用。