Immune cell signaling shapes lung development in mice
Genetic changes that heightened natural killer cell activity impaired normal lung development but protected newborn mice exposed to high oxygen.
Limit: Aging-related effects of altering senescent-cell removal were not measured
Edited by Boris Djordjevic · AgingResearch.News
In mice, experiments tested how transforming growth factor-beta, a signaling protein, affected natural killer cells during lung development after birth. These immune cells can remove senescent cells, which have stopped dividing. Researchers deleted a receptor that allows natural killer cells to respond to the protein.
Newborn mice with the deletion had a lower density of small lung arteries and impaired formation of air sacs. Their natural killer cells removed too many senescent cells lining blood vessels. This heightened activity harmed normal lung development but protected mice exposed to high oxygen. In the high-oxygen model, a compound called HCW9218 prevented senescent cell buildup and rescued lung development. Separately, lung tissue from human infants with bronchopulmonary dysplasia, a disease of newborn lung development, showed excessive transforming growth factor-beta signaling and impaired natural killer cell killing activity.
Why it matters
For aging research on senescent cells, the work raises a question about how to regulate their removal without disrupting tissue function.
Caveats
These experiments tested newborn lung development in mice, not aging or treatment in infants. The human tissue findings did not show whether targeting this signaling would benefit infants.
- HCW9218
- TGFBR2
- Cell killing (cytotoxicity)
- Bronchopulmonary dysplasia
- Lung natural killer cell infiltration
- Mice
The paper
Natural Killer Cell TGF-β Signaling Regulates Postnatal Lung Development
Queen's University
Circulation Research, Oct 27, 2026, Open access
