Fig. 4: Alveolar epithelial repair along the severity continuum.

The regeneration of alveolar tissue and restoration of function is essential for survival following a severe respiratory infection. Recent studies have demonstrated that the extent and severity of influenza virus infection determines the quality of alveolar epithelial repair. Repair by self-renewing type II alveolar cells occurs during less severe infection and is efficient. During infection with extensive tissue damage when type II alveolar cells are ablated, additional epithelial progenitor cells (p63⁻ and p63⁺) mobilize to mediate repair. WNT and NOTCH signalling pathways determine localized differentiation of these progenitor cells. In severe damage, mobilization of p63⁺ progenitors can result in dysplastic alveolar repair characterized by the formation of cyst-like structures with high expression of Krt5 leading to reduced lung function. This dysplastic repair may lead to persistent lung dysfunction.