Innate helper type-2 cells in allergic lung

过敏性肺中的先天辅助2型细胞

• 批准号: 8395783
• 负责人: Richard M Locksley
• 金额: $ 41.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8395783
• 关键词: Allergens; Allergic; Allergic Disease; Aspergillus; Asthma; Attention; Biological Models; Caring; Cell Wall; Cell physiology; Cells; Childhood; Chitin; Chronic; Collaborations; Communities; Complex; Dermatophagoides Antigens; Disease; Epithelial; Epithelium; Evaluation; Extrinsic asthma; Grant; Health Care Costs; Homeostasis; Human; Immune; Immune response; Immunity; Immunohistochemistry; In Situ; Individual; Infection; Inflammation; Inflammatory; Interleukin-13; Interleukin-4; Interleukin-5; Intervention; Irrigation; Lead; Lung; Lung Inflammation; Lymphocyte; Mediating; Mus; Nippostrongylus; Patients; Phenotype; Physiological; Population; Positioning Attribute; Principal Investigator; Process; Reagent; Reporter; Research Personnel; Rest; Role; Sampling; Sorting - Cell Movement; Structure of parenchyma of lung; Subgroup; Th2 Cells; Tissues; United States; asthma prevention; cell type; cytokine; eosinophil; insight; macrophage; novel; programs; response

Asthma is a complex inflammatory disease thought to reflect a dysregulated Immune state established at the epithelial interface in the lung. Although subgroups of patients with different types of Inflammation have been described, allergic asthma, as represented by increased numbers of innate and adaptive IL-4/IL-13- expressing cells, remains highly prevalent. Despite this Insight, understanding the process(es) by which allergic asthma is Initiated will require studies in mice, where recent findings Implicate crosstalk between the lung epithelia and innate immune cells. An innate non-B, non-T, non-NK lymphocyte population present in mice and humans has gained attention through the capacity to respond to epithelial cytokines IL-25 and IL- 33 by release of large amounts of IL-13 and IL-5. Using cytokine reporter mice that accurately function-mark immune cells, we have succeeded in tracking and deleting these cells, which we designate innate helper type-2 or iH2 cells, through their capacity to generate either of these cytokines. Given the central role of IL- 13 and IL-5 In mediating tissue alterations important in asthma and allergic immunity, we propose two specific alms to study the function ofthese cells in allergic lung Inflammation. Specific Aim 1. To establish lineage and function marking of iH2 cells In order to reveal their quantitative contributions to allergic lung immunity during physiologic challenges and to compare this with cytokine- mediated activation. Specific Aim 2. To assess the functional requirements for IH2 cells during allergic challenges and In immune homeostasis, and to examine the physical positioning ofthese cells in lung tissues In situ. Insights from these two Specific Alms will be used to guide the choices of probes and profiles that will enable the study ofthese cells In bronchoaiveolar lavage and airway samples collected from patients with allergic asthma. (LAY SUMMARY). Asthma remains the most prevalent chronic debilitating disease of childhood and a major contributor to health care costs in the United States. These studies seek to understand the early steps required to generate an inflammatory lung response resembling asthma using model systems In mice.

哮喘是一种复杂的炎症性疾病，被认为反映了一种在 肺内的上皮界面。尽管患有不同类型炎症的患者亚组 已有研究表明，过敏性哮喘表现为先天和获得性IL-4/IL-13数量的增加- 表达细胞，仍然非常普遍。尽管有这种洞察力，但通过以下方式理解过程 过敏性哮喘的启动需要在小鼠身上进行研究，最近的发现表明 肺上皮细胞和天然免疫细胞。先天非B、非T、非NK淋巴细胞群存在于 小鼠和人类通过对上皮性细胞因子IL-25和IL-25的反应能力而获得关注 33通过释放大量的IL-13和IL-5。使用准确功能标记的细胞因子报告小鼠 免疫细胞，我们已经成功地跟踪和删除了这些细胞，我们将这些细胞称为先天助手 类型2或IH2细胞，通过它们产生这两种细胞因子的能力。鉴于IL的核心作用- 13和IL-5在介导哮喘和过敏性免疫中重要的组织改变中的作用，我们提出了两个 研究这些细胞在过敏性肺部炎症中的功能。 具体目的1.建立IH2细胞的谱系和功能标记，以揭示其数量 在生理挑战期间对变态反应性肺免疫的贡献，并与细胞因子进行比较- 中介激活。 具体目标2.评估IH2细胞在过敏挑战和免疫过程中的功能需求 动态平衡，并原位检测这些细胞在肺组织中的物理位置。 来自这两个特定ALM的见解将用于指导探测器和配置文件的选择 能够研究从慢性支气管炎患者的支气管肺泡灌洗液和呼吸道样本中收集的这些细胞 过敏性哮喘。 (版面摘要)。哮喘仍然是儿童最常见的慢性衰弱疾病，也是主要的 美国医疗保健费用的贡献者。这些研究试图了解早期的步骤 在小鼠的模型系统中产生类似哮喘的炎性肺反应所需的。