The lung mesenchyme in development, regeneration, and fibrosis

Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular compartments of the lung. During embryonic and postnatal lung development, mesenchyme-derived signals instruct epithelial budding, branching morphogenesis, and subsequent structural and functional maturation. Later during adult life, the mesenchyme plays divergent roles wherein its balanced activation promotes epithelial repair after injury while its aberrant activation can lead to pathological remodeling and fibrosis that are associated with multiple chronic pulmonary diseases, including bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this Review, we discuss the involvement of the lung mesenchyme in various morphogenic, neomorphogenic, and dysmorphogenic aspects of lung biology and health, with special emphasis on lung fibroblast subsets and smooth muscle cells, intercellular communication, and intrinsic mesenchymal mechanisms that drive such physiological and pathophysiological events throughout development, homeostasis, injury repair, regeneration, and aging.

Automated summary

Mesenchymal cells located at the interface between the epithelial lining and the stroma play crucial roles in lung development, repair, and disease progression. They instruct the formation and maturation of lung structures during embryonic and postnatal stages, and can either promote or contribute to pathological remodeling and fibrosis in adulthood. This review focuses on the involvement of lung mesenchyme, particularly fibroblast and smooth muscle cell subsets, in various aspects of lung biology and health, including intercellular communication and intrinsic mechanisms throughout development, homeostasis, injury repair, regeneration, and aging.