Alveolar cells help restore the bronchiolar lining after injury in mice

Alveolar cells help restore the bronchiolar lining after injury in mice

In a Nature paper published on 7 October, researchers used distinct genetic labels to mark cells in mouse alveoli and bronchioles. The cells and their descendants retained these labels. After chemical injury, some alveolar cells gave rise to new cells in the bronchioles. The experiments also traced the signals that guide this transition.

Alveoli are small air sacs in the lungs where blood takes up oxygen. Bronchioles carry air to them. Alveolar type 2 (AT2) cells maintain the alveoli. The bronchiolar lining includes club cells, which produce protective secretions.

The previous genetic label marked both AT2 cells and BASC, rare stem cells at the junction between alveoli and bronchioles. The new labeling scheme gave these groups distinct labels, allowing the researchers to trace each group's contribution separately.

Four weeks after chemical injury, 52% of the regenerated club cells had originated from AT2 cells. BASC accounted for another 27%, and pre-existing club cells for 15%. AT2 descendants also appeared in the bronchioles as ciliated cells, which move mucus along the airways.

During repair, AT2 cells first moved toward the bronchiole, and some then became club cells. Immune cells near the damaged bronchiole released the protein SPP1, which signaled AT2 cells to move toward the injury. AT2 cells detected this signal through integrin β1, a receptor protein on the cell surface. Surviving ciliated cells provided a JAG1 signal that activated the Notch pathway and directed AT2 cells to become club cells. In separate experiments, blocking SPP1 or integrin β1 reduced AT2 cell movement, while interfering with Notch reduced club cell formation.

In this mouse model, cells from the gas-exchange region helped repair a neighboring part of the lung.