The balance and distribution of epithelial cell types is required to maintain tissue homeostasis. In the lung, perturbations of this balance are hallmarks of human respiratory diseases, including goblet cell metaplasia and enhanced mucus secretion in asthma and chronic obstructive pulmonary disease. We found that inflammatory cytokine treatment resulted in a skewing of basal cell differentiation towards a goblet cell fate, culminating in enhanced mucus production. We identified Notch2 as a key node required for cytokine-induced goblet cell metaplasia in vitro and in vivo Inhibition of Notch2 prevents goblet cell metaplasia induced by a broad range of stimuli, which is a hallmark of many respiratory diseases.
