Cellular dynamics in chronic lung disease: the neglected B cell axis

慢性肺病的细胞动力学：被忽视的 B 细胞轴

• 批准号: MR/X03383X/1
• 负责人: Madhvi Menon
• 金额: $ 183.67万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX03383X%2F1
• 关键词: Cellular; dynamics; chronic; lung; disease

The healthy lung contains only sparse immune cells to allow the physical properties necessary for efficient gas exchange and maintain its critical functions. In chronic lung diseases, such as chronic obstructive lung disease (COPD), immune cell infiltrates expand, persist and contribute to defective lung function. As a result, the lung does not return to its original state, and this can have long-term consequences for the patient. COPD is the third leading cause of death worldwide, with no available treatments to delay disease progression. Therefore, developing novel therapeutic strategies for improved disease management is a global priority. Recent studies have focussed on understanding the profile of lung-infiltrating immune cells and their contribution to COPD. Remarkably, knowledge of B cells has lagged far behind that of other immune cells, despite their accumulation and persistence in the COPD lung. This UKRI FLF aims to uncover how B cells promote COPD pathogenesis. Do lung-infiltrating B cells promote tissue inflammation and airway remodelling? Do these aberrant B cell responses associate with disease severity? Can we harness novel pathways involved to develop improved treatment approaches for patients? To address these central questions, I will study in detail the interactions between B cells and their surrounding cells and matrix, to understand how these communications either exacerbate or limit disease.Using freshly isolated immune cells and tissue sections, as well as mouse models of COPD, I aim to ask the following key research questions:- Which aspects of B cell responses in COPD patients associate with disease severity? - Can we identify a molecular signature of COPD-associated B cells in the lung and periphery of COPD patients?- How do interactions between B cells and the surrounding lung microenvironment influence disease outcomes? - Can we ameliorate disease by targeting novel pathways driving B cell dysfunction?This work will be done at The University of Manchester within the world-leading Lydia Becker Institute of Immunology and Inflammation in collaboration with clinicians and pathologists at Manchester University NHS Foundation Trust, as well as my research partners in the UK and overseas. Improved understanding of B cells in COPD could open novel therapeutic avenues for better disease management. These findings may also benefit patients with other chronic lung diseases, such as asthma.

健康的肺仅包含稀疏的免疫细胞，以允许有效的气体交换所需的物理特性并保持其关键功能。在慢性肺部疾病（例如慢性阻塞性肺部疾病（COPD））中，免疫细胞浸润扩展，持久并导致肺功能缺陷。结果，肺部不会恢复其原始状态，这可能会对患者产生长期后果。 COPD是全球死亡的第三大主要原因，没有可用的治疗方法来延迟疾病的进展。因此，制定新的改善疾病管理的治疗策略是全球优先事项。最近的研究集中在理解肺部浸润免疫细胞及其对COPD的贡献的特征。值得注意的是，尽管B细胞在COPD肺中积累和持久性，对B细胞的知识却远远落后于其他免疫细胞的知识。该乌克里FLF旨在发现B细胞如何促进COPD发病机理。肺部浸润B细胞是否会促进组织炎症和气道重塑？这些异常B细胞反应是否与疾病严重程度相关？我们可以利用涉及的新型途径来开发改进的患者治疗方法吗？为了解决这些核心问题，我将详细研究B细胞及其周围细胞与基质之间的相互作用，以了解这些通信如何加剧或限制疾病。使用新鲜隔离的免疫细胞和组织切片以及COPD的小鼠模型，我的目标是询问以下关键研究问题： - COPD患者与疾病严重性的B细胞反应的哪些方面？ - 我们可以确定COPD患者的肺和周围的COPD相关B细胞的分子特征吗？ - B细胞与周围肺微环境之间的相互作用如何影响疾病结果？ - 我们可以通过针对驱动B细胞功能障碍的新途径来减轻疾病吗？这项工作将在曼彻斯特大学与曼彻斯特大学NHS Foundation Trust的临床医生和病理学家合作的曼彻斯特大学进行，莱迪亚·贝克（Lydia Becker）免疫学研究所和炎症。提高对COPD中B细胞的了解可以为更好的疾病管理开放新型的治疗途径。这些发现也可能使患有其他慢性肺部疾病的患者（例如哮喘）受益。