Department of Microbiology, Immunology, and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.
Department of Microbiology, Immunology, and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.
J Allergy Clin Immunol. 2024 Sep;154(3):631-643. doi: 10.1016/j.jaci.2024.04.021. Epub 2024 May 3.
The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR).
We aimed to study basal cell subtypes in AR and healthy controls.
Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite-allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally.
The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air-liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells.
The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR.
气道上皮的完整性由气道基底细胞守护，这些细胞作为祖细胞，在受伤时修复伤口。基底细胞是一个异质群体，其行为的特定变化与慢性屏障破坏有关，而在变应性鼻炎（AR）中，这些机制尚未得到详细研究。
我们旨在研究 AR 和健康对照者中的基底细胞亚型。
对非变应性和屋尘螨变应性 AR 患者的鼻上皮进行单细胞 RNA 测序（scRNA-Seq），以揭示基底细胞的多样性，并确定与过敏相关的改变。通过流式细胞术、免疫荧光染色和使用原代基底细胞的体外实验，在蛋白质水平和功能上验证表型发现。
scRNA-Seq、流式细胞术和免疫荧光染色表明，基底细胞在鼻上皮中丰富且异质存在，提示存在特化的亚型。与对照组相比，AR 上皮中的总基底细胞分数增加。scRNA-Seq 表明，AR 上皮中缺失了潜在有益的基底细胞，而与过敏相关的基底细胞激活群体更为突出。此外，我们的体外增殖、伤口愈合测定和气液界面培养表明，与非变应性基底细胞相比，AR 相关的基底细胞的祖细胞能力发生了改变。
鼻基底细胞群体丰富多样，并在 AR 中向疾病状态转变。潜在保护亚型的缺失和促炎群体的增加表明，基底细胞是维持 AR 上皮屏障缺陷的重要参与者。
