Allergic inflammation and Transcriptional Regulation in Th9 cells

过敏性炎症和 Th9 细胞的转录调控

基本信息

批准号：
10521266
负责人：
MARK H KAPLAN
金额：
$ 56.49万
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：
2005
资助国家：
美国
起止时间：
2005-03-15 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521266
关键词：
ATAC-seq Acute Allergens Allergic Allergic Disease Allergic inflammation Anaphylaxis Aspergillus fumigatus Asthma Attenuated CD4 Positive T Lymphocytes Cell Differentiation process Cell physiology Cells Chronic Chronic Disease Clinical Trials Communication Cost of Illness Data Development Disease model Effector Cell Environment Eye Food Hypersensitivity Funding Gene Expression Genetic Transcription Goals Grant Health Health Care Costs Helper-Inducer T-Lymphocyte Hematopoietic Hypersensitivity IL9 gene IRF4 gene Immune response In Vitro Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Interleukin-13 Interleukin-4 Interleukin-9 Lung Lymphoid Cell Maintenance Mediating Memory Modeling Mutant Strains Mice Organ Pathogenicity Patients Phenotype Population Production Productivity Regulation Regulatory Element Rest Role Source Structure of parenchyma of lung Symptoms System T cell response T memory cell T-Lymphocyte Testing Th2 Cells Tissues Transcriptional Regulation Tumor Immunity Ulcerative Colitis United States allergic airway disease cell type conditional mutant cytokine human model in vivo mouse model response seasonal allergies single-cell RNA sequencing tool transcription factor transcriptome

项目摘要

PROJECT SUMMARY – Regulation of Allergic inflammation by IL-9-secreting T cells Interleukin-9 (IL-9) is a pleuripotent cytokine that leads to altered gene expression and cellular function in hematopoietic and structural cell populations. IL-9 is most efficiently produced by innate lymphoid cells, and a specialized subset of T helper cells termed Th9 cells. Importantly, IL-9 has a role, in both humans and mouse models, in asthma, food allergy, ulcerative colitis, and anti-tumor immunity. In the previous funding period of this grant we have made considerable progress in understanding the regulation of the Il9 gene and the transcription factors that are involved in controlling Il9 gene expression. As we defined systems for best analyzing IL-9-secreting T cells in vivo, we observed that in a model of chronic allergen exposure, IL-9- producing CD4+ T cells were in the tissue resident memory (Trm) population. We further observed that the IL- 9-secreting Trm population was stable in the absence of allergen exposure and was instrumental in mediating the inflammatory response to allergen challenge after a period of ‘rest’ from allergen exposure. Blocking IL-9 during this post-rest challenge significantly diminished the inflammatory response. In this renewal application, we will define the identity of the IL-9-secreting T cells, determine the transcription factors that are required for their development, and identify the cytokines that are important for their development, maintenance, and effector function. As the CD4+ Trm population in allergic inflammation has not been characterized and this population is likely important in the context of intermittent allergen exposure as occurs in seasonal allergies, the proposed studies could have a foundational impact on understanding how CD4+ Trm impact allergic disease.

项目摘要 - 通过分泌IL-9的T细胞来调节过敏性炎症白介素-9（IL-9）是一种胸膜细胞因子，导致基因表达和细胞功能改变造血和结构细胞种群。 IL-9最有效地由先天淋巴样细胞产生，A T辅助细胞的专门子集称为Th9细胞。重要的是，IL-9在人类和小鼠中都有作用模型，哮喘，食物过敏，溃疡性结肠炎和抗肿瘤免疫。在上一个资金期我们在理解IL9基因的调节和控制IL9基因表达的转录因子。当我们定义最佳系统时分析了分析IL-9分泌T细胞的体内，我们观察到，在慢性过敏原暴露模型中，IL-9-- 产生CD4+ T细胞在组织居民记忆（TRM）中。我们进一步观察到IL- 在没有过敏原暴露的情况下，9分泌的TRM种群是稳定的，并且有助于介导过敏原暴露的“休息”一段时间后，对过敏原挑战的炎症反应。阻止IL-9 在此后期，挑战大大减少了炎症反应。在此续签应用中，我们将定义分泌IL-9分泌T细胞的身份，确定转录因子它们的开发，并确定对它们的开发，维护以及效应子功能。由于过敏注射中的CD4+ TRM种群尚未表征，因此在季节性过敏中发生的间歇过敏原暴露的情况下，人口可能很重要提出的研究可能对了解CD4+ TRM如何影响过敏有基本的影响疾病。