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
基本信息
- 批准号:MR/X03383X/1
- 负责人:
- 金额:$ 183.67万
- 依托单位:
- 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:
- 关键词:
项目摘要
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.
健康的肺部仅含有稀疏的免疫细胞,以提供有效气体交换和维持其关键功能所需的物理特性。在慢性肺部疾病中,例如慢性阻塞性肺病(COPD),免疫细胞浸润会扩大、持续并导致肺功能缺陷。结果,肺部无法恢复到原来的状态,这可能会给患者带来长期后果。慢性阻塞性肺病是全球第三大死亡原因,目前尚无可用的治疗方法来延缓疾病进展。因此,开发新的治疗策略以改善疾病管理是全球的首要任务。最近的研究重点是了解肺部浸润免疫细胞的概况及其对慢性阻塞性肺病的贡献。值得注意的是,尽管 B 细胞在 COPD 肺部积累并持续存在,但对 B 细胞的了解远远落后于其他免疫细胞。 UKRI FLF 旨在揭示 B 细胞如何促进 COPD 发病机制。肺部浸润 B 细胞是否会促进组织炎症和气道重塑?这些异常的 B 细胞反应与疾病严重程度相关吗?我们能否利用新的途径来为患者开发改进的治疗方法?为了解决这些核心问题,我将详细研究 B 细胞与其周围细胞和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。使用新鲜分离的免疫细胞和组织切片,以及 COPD 小鼠模型,我的目的是提出以下关键研究问题:- COPD 患者 B 细胞反应的哪些方面与疾病严重程度相关? - 我们能否识别 COPD 患者肺部和外周 COPD 相关 B 细胞的分子特征? - B 细胞与周围肺部微环境之间的相互作用如何影响疾病结果? - 我们能否通过针对驱动 B 细胞功能障碍的新途径来改善疾病?这项工作将在世界领先的 Lydia Becker 免疫学和炎症研究所的曼彻斯特大学与曼彻斯特大学 NHS 基金会信托基金的临床医生和病理学家合作完成,以及我在英国和海外的研究伙伴。提高对 COPD 中 B 细胞的了解可以为更好的疾病管理开辟新的治疗途径。这些发现也可能使患有其他慢性肺部疾病(例如哮喘)的患者受益。
项目成果
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