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Th9 cells in immediate hypersensitivity

速发型超敏反应中的 Th9 细胞

基本信息

批准号：
10083170
负责人：
MARK H KAPLAN
金额：
$ 39.38万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10083170
关键词：
Active Immunization Acute Address Allergens Allergic Allergic Disease Allergic inflammation Allergy to peanuts Anaphylaxis Asthma Attenuated Cell Differentiation process Cell physiology Cells Cessation of life Chronic Chronic Disease Cost of Illness Data Development Disease Genes Goals Health Health Care Costs Helper-Inducer T-Lymphocyte Hypersensitivity IL9 gene IgE Immediate hypersensitivity Impairment Inflammation Inflammation Mediators Inflammatory Interleukin-4 Interleukin-9 Intervention Lead Link Lung Inflammation Mediating Modeling Mus Organ Passive Immunization Pathway interactions Patients Phenotype Production Productivity Reaction Role Serum Signal Transduction Skin Symptoms T-Lymphocyte Testing Therapeutic Intervention Transgenic Organisms United States Urticaria Work allergic airway inflammation allergic response asthmatic patient base crosslink cytokine mast cell new therapeutic target novel response transcription factor

项目摘要

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.

项目摘要/摘要 – 速发型超敏反应中的 Th9 细胞 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。 T辅助子集的发展由网络控制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。该提案重点关注最近发现的 T 辅助细胞子集，响应 TGF 和 IL-4 而分化的 Th9 细胞。在我们的初步数据中，我们已经确定了过敏性气道炎症中肥大细胞积累和功能需要 Th9 细胞。有趣的是，我们已经确定了 Th9 细胞在促进即时超敏反应中的作用。在两个目标中在该提案中，我们解决了对于理解 Th9 依赖性肥大细胞活性至关重要的基本问题。在第一个目标是使用过敏原确定速发型超敏反应对 Th9 细胞的要求 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，我们将确定 Th9 细胞如何调节肥大细胞积累和激活，并确定哪个方面是 Th9 依赖性肥大细胞功能所需。这些目标将共同定义涉及以下方面的新机制： Th9 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干预途径。