Allergic inflammation and Transcriptional Regulation in Th9 cells

过敏性炎症和 Th9 细胞的转录调控

• 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
• 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

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。