Scientists at Mayo Clinic have uncovered a molecular “switch” inside lung cells that determines whether those cells focus on healing damaged tissue or defending against infection. The discovery offers new insight that could shape future regenerative treatments for chronic lung diseases.

“We were surprised to find that these specialized cells cannot do both jobs at once,” says Douglas Brownfield, Ph.D., senior author of the study published in Nature Communications. “Some commit to rebuilding, while others focus on defense. That division of labor is essential. And by uncovering the switch that controls it, we can start thinking about how to restore balance when it breaks down in disease.”

The Dual Role of Alveolar Type 2 (AT2) Cells
The research centers on alveolar type 2 (AT2) cells, which play a critical role in lung health. These cells help maintain the air sacs by producing proteins that keep them open during breathing. At the same time, they serve as reserve stem cells capable of replacing alveolar type 1 (AT1) cells, the thin cells that form the surface where oxygen passes into the bloodstream.

For years, researchers have observed that AT2 cells often fail to regenerate effectively in conditions such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and severe viral infections including COVID-19. However, the biological reason these cells lose their regenerative ability had not been fully understood.