Chronic obstructive pulmonary disease (COPD) is characterized by small airway inflammation and obstruction as well as infectious exacerbations. A defect in polymeric immunoglobulin receptor (pIgR) expression has been reported, resulting in secretory IgA-deficient areas that promote persistent inflammation. However, mechanisms linking pIgR defect and altered repair of small airways remain elusive. We hypothesized that pIgR could identify club cells with regenerative potential in the human distal lung.

Paraffin sections (1 section/lung) from 9 control lungs (unused donor lungs) and 7 severe COPD lungs (explants) were stained by multiplex immunofluorescence for pIgR, CC16 and Ki67, followed by quantification in small airways (defined histologically as terminal bronchioles) using Visiopharm®.

Most club (CC16+) cells expressed pIgR in control lungs, while this feature was decreased in COPD (78.4% [57.8–88.8], median [IQR], in controls vs. 54% [40–72.7] in COPD, P=0.049). In addition, based on expression of CC16 among proliferating (Ki67+) cells (84% [81.1–95.6] in controls vs. 91.3% [73–100] in COPD), most proliferating epithelial cells in small airways consisted of club cells. Finally, among proliferating club (Ki67+CC16+) cells, pIgR expression was strongly decreased in COPD (15% [3.0–24.9] in controls vs. 0.4% [0–1.4] in COPD, P=0.0046) (Fig. 1).

These pilot data confirm [1 Am J Respir Cell Mol Biol 2022 ; 10.1165/rcmb.2021-0548OC[published online ahead of print].

Cliquez ici pour aller à la section Références] that club cells of human small airways display a robust expression of pIgR, and suggest that the pool of proliferating club cells expressing this marker is almost lost in patients with severe COPD. Further studies are needed to assess the role of pIgR in club cells.