A clean sweep: mucin bundles clear the airway

Mucostasis and small airway plugging lead to chronic infection, hyperinflammation, and a spiral of progressive lung damage in cystic fibrosis (CF), ultimately causing bronchiectasis and pulmonary function decline [1]. Even in the absence of bacterial infection, mucus accumulation can lead to inflammatory upregulation, resulting in lung damage despite bacterial eradication [2]. Airway mucus has been postulated to be overproduced and inefficiently transported in CF [3, 4]. In human epithelial cells as well as multiple animal models of CF, mucus is hyperviscous and abnormally elastic [5–9]. In CF pigs, mucus is also aberrantly tethered to the gland duct openings, a factor which may underlie the propensity for CF mucus to spend less time in motion than in the normal condition [10]. While the mucus layer of the airway surface liquid (ASL) contains numerous proteins, surfactants, antibacterial proteases and anti-proteases [11], its major components are mucins [12]. Mucins are large glycopolymers that can either be tethered to the epithelium or secreted into the lumen as gel-forming polymers, as is the case with MUC5B and MUC5AC [13]. While the roles of individual mucins, namely MUC5B and MUC5AC, have been well identified in other disease states, such as asthma and bacterial infections, it is less well delineated how they are overproduced or dysregulated in CF [13]. Furthermore, in CF, in the absence of adequate bicarbonate concentrations, mucins may not exist in the appropriate conformation, a potential cause of many of these abnormalities [14, 15]. Yet, despite all that is known about mucins and mucus in CF and other muco-obstructive diseases, a means to correcting these abnormalities and restoring normal mucus clearance has yet to be identified. Mucus bundles are important for airway clearance and are regulated by cholinergic stimulus