Th9 cells in immediate hypersensitivity

项目总结/摘要-速发型超敏反应中的Th 9细胞 辅助性T细胞亚群调节炎症性疾病，包括过敏性肺的发展 与哮喘有关的炎症。辅助性T细胞亚群的发育受一个免疫调节网络的控制， 这些转录因子促进细胞因子和其他与T细胞活化能力相关的基因的表达， 辅助细胞促进疾病。这项建议的重点是最近确定的T辅助细胞的子集， Th 9细胞响应于TGF β 1和IL-4而分化。在我们的初步数据中， 过敏性气道炎症中肥大细胞积累和功能对Th 9细胞的需求有趣的是， 我们已经确定了Th 9细胞在促进速发型超敏反应中的作用。在两个目标中， 我们的这个提议解决了对于理解Th 9依赖性肥大细胞活性至关重要的基本问题。在 第一个目的是确定使用过敏原的速发型超敏反应对Th 9细胞的需求 IgE依赖性肥大细胞功能的致敏和被动转移模型。在第二个目标中， 确定Th 9细胞如何调节肥大细胞的积累和激活，并确定哪个方面是 Th 9依赖性肥大细胞功能所必需的。这些目标将共同确定新的机制， Th 9依赖性急性过敏原反应。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.