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Secretion of mucus into the airway lumen is a fundamental host defense mechanism that enables trapping of pathogens and other inhaled particles and their subsequent removal from the airways via mucociliary escalator. The numbers of mucus-producing goblet cells are tightly controlled to secure the baseline mucin levels on the airway surface, while preventing mucus plugging of small bronchioles, where these cells are rare or absent.1 Maintaining a proper number of mucus-producing cells in the airways is a function of tissue-resident basal stem cells, which, under control of physiological or injury-associated signals, regenerate airway epithelium with a distinct proportion of basal, ciliated and secretory cells.
Increase in goblet cell numbers or mucous cell hyperplasia (MCH) occurs in response to pathogens, oxidants, toxins, particles and cigarette smoke, leading to a transient mucus hypersecretion that normally disappears after the stimuli are no longer present. In chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), overproduction of mucus persists over time contributing to clinical symptoms. Long-term maintenance of MCH, a morphological basis of chronic mucus hypersecretion in these conditions, can result from sustained activation of airway basal cells or their progenies by disease-associated signals that promote their excessive differentiation toward mucus-producing cells.
Several pathways are known to promote MCH by modifying the fate of airway basal cells. Airway inflammation driven by T helper (Th)2 cells, characteristic for asthma, promotes MCH via interleukin (IL)-13 that shifts the fate of airway basal cell-derived progenitors to the goblet cell lineage by activating Notch signalling required for differentiation of airway basal cells into secretory cells.2 3 Th17-derived IL-17 associated with neutrophilic airway inflammation in severe asthma and COPD exacerbations can promote MCH via Notch2-dependent signalling in airway basal cells.3
Cigarette smoking, the major risk factor for COPD, can promote MCH independent of inflammation, by …
Contributors RS is the sole contributor.
Funding This study was funded by National Heart, Lung, and Blood Institute (R01HL123544, R01HL127393).
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Commissioned; externally peer reviewed.
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