  In cystic fibrosis (CF), impaired mucociliary clearance leads to chronic
infection and inflammation. However, cilia beating features in a CF altered
environment, consisting of dehydrated airway surface liquid layer and abnormal
mucus, has not been fully characterized. Furthermore, acute inflammation is
normally followed by an active resolution phase requiring specialized
pro-resolving lipid mediators (SPMs) and allowing return to homeostasis.
However, altered SPMs biosynthesis have been reported in CF. Here, we explored
cilia beating dynamics in CF airways primary cultures and its response to the
SPMs, resolvin E1 (RvE1) and lipoxin B4 (LXB4). Human nasal epithelial cells
(hNECs) from CF and non-CF donors were grown at air-liquid interface. The
ciliary beat frequency, synchronization, orientation, and density were analyzed
from high-speed video-microscopy using multiscale Differential Dynamic
Microscopy algorithm and an in-house developed method. Mucins and ASL layer
height were studied by RT-qPCR and confocal microscopy. Principal component
analysis showed that CF and non-CF hNEC had distinct cilia beating phenotypes,
which was mostly explained by differences in cilia beat organization rather
than frequency. Exposure to RvE1 (10 nM) and to LXB4 (10 nM) restored a non-CF
like cilia beating phenotype. Furthermore, RvE1 increased the airway surface
liquid (ASL) layer height and reduced the mucin MUC5AC thickness. The
calcium-activated chloride channel, TMEM16A was involved in RvE1 effect on
cilia beating, hydration and mucus. Altogether, our results provide evidence
for defective cilia beating in CF airway epithelium and a role of RvE1 and LXB4
to restore the main epithelial functions involved in the mucociliary clearance.
