Investigation of memory B cell response in asthmatic lungs.

哮喘肺部记忆 B 细胞反应的研究。

• 批准号: 10303811
• 负责人: Yee Ling Wu
• 金额: $ 22.3万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303811
• 关键词: Adoptive Transfer; Airway Disease; Allergens; Anatomy; Antibodies; Antibody Response; Antigens; Asthma; B-Lymphocyte Subsets; B-Lymphocytes; Biological Assay; Biology; Blood Circulation; Cells; Characteristics; Cues; Disease; Exhibits; Exposure to; Extrinsic asthma; Generations; Goals; Hypersensitivity; IgE; Image; Immune; Immunoglobulin Class Switching; Immunologics; In Situ; In Vitro; Infection; Inflammation; Inflammatory; Inhalation; Intercept; Investigation; Knowledge; Life; Local Therapy; Lung; Mediating; Memory; Memory B-Lymphocyte; Microscopy; Molecular; Molecular Profiling; Monitor; Mus; Pathogenicity; Patients; Phenotype; Plasma Cells; Population; Prevalence; Prevention; Production; Reporter; Residencies; Resolution; Respiratory Mucosa; Respiratory Tract Infections; Respiratory distress; Role; Source; Specificity; Structure of parenchyma of lung; Symptoms; Systemic disease; Tissues; adaptive immune response; airway hyperresponsiveness; airway inflammation; allergic airway disease; asthmatic; cell type; chronic inflammatory disease; chronic inflammatory lung disease; constriction; effective therapy; falls; in vivo; influenzavirus; mouse model; neutralizing antibody; novel marker; prevent; pulmonary function; recruit; response; single-cell RNA sequencing; transcriptomics

Project Summary/Abstract Allergic asthma is a chronic inflammatory disease of the lungs without cures and effective preventions. Allergen-specific IgE antibodies drive inflammation, airway constriction, and respiratory distress in patients with allergic asthma. Evidence for the existence of a local cellular source of pathogenic IgE in the airway is mounting. However, the precise identity of these cells as well as mechanisms for their localization within the asthmatic lung remain elusive. Using a mouse model of airway hypersensitivity, we have identified a lung- localized population of memory B cell that persists beyond the resolution of inflammation, but rapidly expands upon allergen re-challenge. We hypothesize that these cells are bona fide lung-resident memory B cells that elicit rapid local IgE responses and maintain long-term airway hypersensitivity. In this study, we will 1) elucidate the mechanisms that recruit MBCs and maintain their long-term tissue residency in asthmatic lungs using complementary immune phenotyping, single-cell transcriptomic and imaging analyses; and 2) investigate how functionally lung-resident MBCs contribute to allergic asthma using in vivo depletion of circulating memory B cells and adoptive transfer studies. This study on understanding the biology and functions of tissue-resident memory B cells in asthmatic lungs is imperative, and may reveal new targets for treating and preventing the progression of allergic asthma and other inflammatory lung conditions.

项目摘要/摘要 过敏性哮喘是一种没有治愈和有效预防的肺部慢性炎症性疾病。 过敏原特异性IgE抗体驱动炎症，气道收缩和呼吸障碍患者 过敏性哮喘。证据表明，气道中存在致病性IgE的局部细胞来源是 安装。但是，这些细胞的精确身份以及它们在其内部的机制 哮喘肺仍然难以捉摸。使用气道超敏反应的小鼠模型，我们已经确定了肺 局部记忆B细胞的局部群体持续超出了炎症的分辨率，但迅速扩展 在过敏原重新挑战上。我们假设这些细胞是真正的肺居民记忆B细胞 引起快速的局部IGE反应并保持长期气道超敏反应。在这项研究中，我们将1） 阐明募集MBC并维持其长期组织居留在哮喘肺中的机制 使用互补的免疫表型，单细胞转录组和成像分析； 2）调查 在功能上使用循环记忆的体内耗竭对肺居民的MBC如何促进过敏性哮喘 B细胞和收养转移研究。这项有关了解组织居民的生物学和功能的研究 哮喘肺中的记忆B细胞是必须的，并且可能揭示了治疗和防止该目标的新目标 过敏性哮喘和其他炎症性肺部状况的进展。