Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease.

Discovery immunology Pub Date : 2023-07-19 eCollection Date: 2023-01-01 DOI:10.1093/discim/kyad009
Stefano A P Colombo, Sheila L Brown, Matthew R Hepworth, Jenny Hankinson, Felice Granato, Semra J Kitchen, Tracy Hussell, Angela Simpson, Peter C Cook, Andrew S MacDonald
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Abstract

The lung is a dynamic mucosal surface constantly exposed to a variety of immunological challenges including harmless environmental antigens, pollutants, and potentially invasive microorganisms. Dysregulation of the immune system at this crucial site is associated with a range of chronic inflammatory conditions including asthma and Chronic Pulmonary Obstructive Disease (COPD). However, due to its relative inaccessibility, our fundamental understanding of the human lung immune compartment is limited. To address this, we performed flow cytometric immune phenotyping of human lung tissue and matched blood samples that were isolated from 115 donors undergoing lung tissue resection. We provide detailed characterization of the lung mononuclear phagocyte and T cell compartments, demonstrating clear phenotypic differences between lung tissue cells and those in peripheral circulation. Additionally, we show that CD103 expression demarcates pulmonary T cells that have undergone recent TCR and IL-7R signalling. Unexpectedly, we discovered that the immune landscape from asthmatic or COPD donors was broadly comparable to controls. Our data provide a much-needed expansion of our understanding of the pulmonary immune compartment in both health and disease.

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人体肺部和血液中循环免疫细胞与组织免疫细胞在健康和疾病期间的表型比较。
肺部是一个动态的粘膜表面,经常暴露在各种免疫挑战之下,包括无害的环境抗原、污染物和潜在的入侵微生物。免疫系统在这一关键部位的失调与一系列慢性炎症有关,包括哮喘和慢性肺阻塞性疾病(COPD)。然而,由于其相对不可接近性,我们对人体肺部免疫区的基本了解十分有限。为了解决这个问题,我们对从 115 名接受肺组织切除术的供体中分离出来的人肺组织和匹配的血液样本进行了流式细胞免疫表型分析。我们详细描述了肺单核吞噬细胞和 T 细胞区系的特征,显示了肺组织细胞和外周循环细胞之间明显的表型差异。此外,我们还发现,CD103 的表达可将肺部 T 细胞区分为近期接受过 TCR 和 IL-7R 信号传导的细胞。意想不到的是,我们发现哮喘或慢性阻塞性肺病供体的免疫状况与对照组大致相当。我们的数据为我们了解健康和疾病中的肺部免疫区提供了亟需的拓展。
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