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.

项目总结/摘要 过敏性哮喘是一种慢性肺部炎症性疾病，无法治愈和有效预防。 过敏原特异性IgE抗体驱动哮喘患者的炎症、气道收缩和呼吸窘迫 过敏性哮喘气道中存在局部细胞源的致病性IgE的证据是 安装。然而，这些细胞的确切身份以及它们在细胞内的定位机制还不清楚。 哮喘肺仍然难以捉摸。使用小鼠气道超敏反应模型，我们已经确定了肺- 局部记忆B细胞群，在炎症消退后持续存在，但迅速扩张 过敏原再激发后。我们假设这些细胞是真正的肺驻留记忆B细胞， 引起快速的局部IgE反应并维持长期的气道超敏反应。在本研究中，我们将（1） 阐明招募MBC并维持其在哮喘肺组织中长期驻留的机制 使用互补免疫表型、单细胞转录组学和成像分析;和2）研究 使用体内循环记忆耗竭功能性肺驻留MBC如何促进变应性哮喘 B细胞和过继转移研究。本研究旨在了解组织驻留的生物学和功能， 哮喘肺中的记忆B细胞是必要的，并可能揭示治疗和预防哮喘的新靶点。 过敏性哮喘和其他炎症性肺病的进展。