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: 10413232
• 负责人: Yee Ling Wu
• 金额: $ 18.57万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413232
• 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 过敏性哮喘是一种慢性肺部炎症性疾病，没有治愈方法和有效的预防措施。 过敏原特异性IgE抗体可导致炎症、呼吸道收缩和呼吸窘迫 过敏性哮喘。呼吸道中存在致病IgE的局部细胞源的证据是 正在安装中。然而，这些细胞的确切身份以及它们在 哮喘肺仍难以捉摸。使用呼吸道过敏的小鼠模型，我们已经识别出一种肺- 局部的记忆B细胞群，持续超过炎症消退，但迅速扩张 在过敏原再次挑战时。我们假设这些细胞是真正的驻肺记忆B细胞 激发快速局部免疫球蛋白E反应并维持长期的呼吸道超敏反应。在这项研究中，我们将1) 阐明在哮喘肺中募集巨噬细胞并维持其长期组织滞留的机制 使用互补免疫表型、单细胞转录和成像分析；以及2)研究 利用体内循环记忆耗竭研究肺功能上的单核细胞如何参与过敏性哮喘 B细胞和过继转移研究。了解组织居留的生物学和功能的研究 哮喘肺部记忆B细胞势在必行，并可能为治疗和预防哮喘提供新的靶点。 过敏性哮喘和其他炎症性肺部疾病的进展。