Th9 cells in immediate hypersensitivity

项目摘要/摘要-Th9细胞处于即刻过敏状态 T辅助细胞亚群调节炎症性疾病，包括过敏性肺的发展 与哮喘相关的炎症。由网络控制的T辅助子集的开发 促进细胞因子和其他与T细胞能力相关的基因表达的转录因子 辅助细胞促进疾病。该建议集中于最近识别的T辅助细胞的子集， Th9细胞对转化生长因子和IL-4的反应而分化。在我们的初步数据中，我们已经确定了一个 过敏性呼吸道炎症对Th9细胞肥大细胞聚集和功能的要求。有趣的是， 我们已经确定了Th9细胞在促进即刻超敏反应中的作用。在两个目标中 在这项提议中，我们解决了对于理解Th9依赖的肥大细胞活动至关重要的基本问题。在……里面 第一个目标是定义Th9细胞对使用变应原的即刻超敏反应的要求 依赖IgE的肥大细胞功能的敏化和被动转移模型。在第二个目标中，我们将 确定Th9细胞如何调节肥大细胞的积累和激活，并确定哪个方面是 Th9依赖的肥大细胞功能所必需的。这些目标将共同定义新的机制，涉及 Th9依赖的急性过敏原反应。这些目标将阐明急性和慢性疾病的新途径 过敏反应，并强调潜在的新的干预途径。

PROJECT SUMMARY / ABSTRACT – Th9 cells in immediate hypersensitivity T helper subsets regulate inflammatory diseases, including the development of allergic lung inflammation associated with asthma. The development of T helper subsets in controlled by a network of transcription factors that promote the expression of cytokines and other genes associated with the ability of a T helper cell to promote disease. This proposal focuses on the most recently identified subset of T helper cells, Th9 cells that differentiate in response to TGF and IL-4. In our preliminary data we have identified a requirement for Th9 cells for mast cell accumulation and function in allergic airway inflammation. Interestingly, we have identified a role for Th9 cells in facilitating immediate hypersensitivity responses. In the two Aims in this proposal we address basic questions that are critical for understanding Th9-dependent mast cell activity. In the first aim we will define the requirement for Th9 cells in immediate hypersensitivity using allergen sensitization and passive transfer models of IgE-dependent mast cell function. In the second Aim we will determine how Th9 cells regulate mast cell accumulation and activation, and determine which aspect is required for Th9-dependent mast cell function. Together, these Aims will define new mechanisms involved in Th9-dependent acute allergen responses. These Aims will elucidate new pathways in acute and chronic allergic responses and highlight potentially new pathways for intervention.