Abstract
Dilation of bronchi and bronchioles caused by destruction and excessive epithelial remodeling is a characteristic feature of bronchiectasis. It is not known how epithelial progenitor cells contribute to these pathologic conditions in peripheral airways (bronchioles) in bronchiectasis. We aimed to explore the expression levels of signature airway progenitor cells in the dilated bronchioles in patients with bronchiectasis. We obtained the surgically resected peripheral lung tissues from 43 patients with bronchiectasis and 33 control subjects. Immunostaining was performed to determine the expression patterns of thyroid transcription factor-1 (TTF-1, for labeling progenitor cells in distal airways), P63 (basal cells), club cell 10 kDa protein (CC10, club cells), and surfactant protein C (SPC, alveolar type II epithelial cells) in epithelium or sub-epithelium. Here, we reported significantly lower percentage of TTF-1+ cells and CC10+ cells, and higher percentage of P63+ cells within the epithelium of dilated bronchioles compared with control bronchioles. In airway sub-epithelium of the dilated bronchioles, epithelial hyperplasia with disarrangement of TTF-1+ cells yielded cuboidal (100%) and columnar (93.0%) type among bronchiectasis patients. Most progenitor cell markers co-localized with TTF-1. The median (the 1st, 3rd quartile) percentage of P63+TTF-1+, CC10+TTF-1+, and SPC+TTF-1+ cells was 16.0% (8.9, 24.0%), 14.5% (7.1, 20.8%), and 52% (40.3, 64.4%), respectively. For cuboidal epithelial hyperplasia, 91.0% (86.5, 94.0%) of areas co-stained with SPC and TTF-1. Columnar epithelial hyperplasia was characterized by TTF-1 co-staining with P63+TTF-1+ and CC10+TTF-1+ cells. Taken together, aberrant proliferation of airway progenitor cells in both epithelium and sub-epithelium are implicated in bronchiectasis.
Highlights
Bronchiectasis is characterized by recurrent infections and heightened inflammatory responses that are responsible for progressive lung injury and irreversible dilatation of bronchi and bronchioles (Boyton and Altmann, 2016)
We have identified two major patterns of epithelial hyperplasia which can be extensively labeled by thyroid transcription factor-1 (TTF-1)+ in sub-epithelium of the dilated bronchioles
Our results provide a basis for promoting epithelial cells (ECs) repair through “normalizing” airway progenitor cells, which might help reverse the trend of bronchiectasis progression
Summary
Bronchiectasis is characterized by recurrent infections and heightened inflammatory responses that are responsible for progressive lung injury and irreversible dilatation of bronchi and bronchioles (Boyton and Altmann, 2016). The pathologic dilatation of bronchioles may co-exist with bronchiectasis of the large to medium-sized airways. Impaired mucociliary clearance and aberrant repair (including hyperplasia) of airway epithelium has recently been implicated in bronchiectasis (Chen et al, 2018). Advances in pathophysiology have provided fundamental insights into the role of airway epithelium in the milieu of recurrent infections and inflammation. Endogenous airway progenitor cells are crucial to lung homeostasis and regeneration because of their self-renewal capacity through differentiation into normal airway epithelial cells (ECs) (Nikolicet al., 2018; Liu et al, 2019). Basal cells (BCs) counts were lower and self-renewal capacity was impaired in Abbreviations: AECII, type II alveolar epithelial cell; BC, basal cell; CC10, club cell 10 kDa protein; DAPI, 4 6-diamidino-2-phenylindole; FEV1, first second percentage; FVC, forced vital capacity; HPF, high power field; HRCT, high-resolution computed tomography; HRP, horseradish peroxidase; IF, immunofluorescent; IHC, immunohistochemistry; SPC, surfactant protein C; TTF-1, thyroid transcription factor-1
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