Airway ciliated cells in adult lung homeostasis and COPD

Abstract

Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD.

FIGURE 1

Cilia are present in the principal lung cell populations. a) The main pulmonary airway cell populations from bronchi (large airways) to alveoli (distal airways), depicting airway epithelial cells (AECs) and mesenchymal cells. b) Representative micrographs showing the specific cell population (numbered 1–6) analysed by immunostainings on formalin-fixed paraffin-embedded non-COPD smoker lung tissue for identification marker (FoxJ1, smooth muscle actin (SMA), p63, vimentin; all green); cilia (Arl13b; red) and cell nuclei (4′,6-diamidino-2-phenylindole (DAPI); blue) as observed on formalin-fixed paraffin-embedded lung tissues. Arrowheads indicate ciliated cells (either motile cilia or primary cilia); dashed lines trace an example of the cell population. Scale bars=25 μm and 5 μm.

FIGURE 2

Structural aspects of primary cilia and motile cilia. The schematic shows the global structure of primary cilia and motile cilia in the respiratory context with a focus on the axoneme and its molecular composition. Figure created using BioRender.com.

FIGURE 3

Primary cilia and motile cilia appear during airway epithelial cell differentiation in vitro. Representative confocal acquisitions from large airway epithelial cell cultures from a non-COPD smoker at ALI-d14 for CK13 (green), cilia (Arl13b; red) and cell nuclei (4′,6-diamidino-2-phenylindole (DAPI); blue). Merged z-projections on two selected areas depicted by orange or purple frames are shown with orthogonal projections (dashed lines). Arrowheads indicate primary cilia (white) and motile cilia (yellow).