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: 8172630
• 负责人: Reen Wu
• 金额: $ 7.6万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172630
• 关键词: Adoptive Transfer; Animals; Asthma; Autoimmune Diseases; CD4 Positive T Lymphocytes; Cell Differentiation process; Cell Lineage; Cells; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Grant; Helper-Inducer T-Lymphocyte; Host Defense; Human Development; In Vitro; Inflammatory; Institution; Interleukin-17; Interleukins; Knowledge; Lung diseases; Mediator of activation protein; Modeling; Monkeys; Mucosal Immunity; National Institute of Environmental Health Sciences; Nature; Pathogenesis; Pilot Projects; Research; Research Personnel; Resources; Role; Source; Stem cells; System; Testing; Umbilical Cord Blood; United States National Institutes of Health; base; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 选择性产生白介素（IL）-17的新型辅助T细胞的新谱系为免疫调节，宿主防御和自身免疫性疾病的发病机理提供了令人兴奋的新见解。对于各种肺部疾病，还记录了IL-17A，IL-17F升高的Th17细胞及其秘密产物。但是，与IL-17和Th17细胞有关的存在的性质以及功能尚不清楚。对于非人类灵长类动物，缺乏有关Th17细胞及其秘密产物在各种疾病和炎症状况中的功能作用的信息。由于非人类灵长类动物猴子是与人类最近的动物，因此必须在体外进行Th17细胞谱系的发展，以将新知识应用于各种疾病。对于CNRPC的呼吸道疾病单元，有一个独特的机会利用自适应转移方法来表征过去30年中NIEHS支持的肺损伤和哮喘模型中Th17细胞及其秘密产物的功能。试点项目应用中的当前假设是Th17细胞谱系的可塑性和功能受粘膜免疫中存在的各种细胞因子和介质的调节。为了检验这一假设，我们将开发一个体外系统，用于非人类灵长类动物TH17细胞与脐带血中存在的祖细胞分化，并研究该细胞谱系对各种细胞因子和介体的反应。我们认为，这是非人类灵长类动物Th17细胞谱系的第一项研究。提出了两个具体目标。目的1是建立一个体外培养系统，非人类灵长类动物可以分化为Th17细胞谱系。第二个目的是检查体外对各种细胞因子的响应Th17细胞分化的可塑性。从这些研究中获得的信息将作为自适应转移实验的基础，以检查Th17细胞在肺部疾病中的作用。