Natural killer cells that live in the lungs can respond quickly to a sugar surge, making them particularly effective.

Trinity College Dublin researchers based at St James’s Hospital have provided important insights into the behavior and metabolic function of a previously largely unknown but crucial natural killer (NK) immune cell residing in the lungs.

Their findings, published today in the journal Proceedings of the National Academy of Sciencesprovide a basis for further exploration of NK cells for the development of future treatments and therapies for various lung diseases, including chronic obstructive pulmonary disease (COPD), cancer and tuberculosis.

The human lung is normally a low glucose environment. However, during infection, glucose becomes readily available and its rapid absorption and metabolism allows immune cells to fight infections. Natural killer (NK) cells are immune cells responsible for ensuring early host defense. NK cells that live long-term in the lungs or other organs are called tissue residents. Prior to this study, the metabolic function of human tissue-resident NK cells in the lungs was largely unknown.

Researchers have shown for the first time that NK cells residing in human lung tissue are metabolically distinct from their counterparts circulating in the blood. The team’s findings show that NK cells residing in the lungs are primed to respond rapidly to increased glucose in the environment, with an increased ability to increase glucose metabolism to generate the materials that NK cells have. needed to mount an effective immune response.

Key findings include:

• Metabolic distinctness: NK cells residing in lung tissue are metabolically distinct from their blood counterparts, demonstrating a unique ability to rapidly metabolize glucose in response to environmental changes, for example during infections.
• Enhanced Glycolytic Capacity: These lung-resident NK cells exhibit higher glycolytic capacity than non-tissue-resident NK cells. This allows them to generate the necessary energy and metabolites more efficiently, enabling a rapid immune response.
• Ready to respond: The metabolic readiness of lung-resident NK cells indicates that they are ready to respond rapidly to increased glucose availability during infections, thereby enhancing their ability to mount an effective immune defense.
• Disease Implications: Understanding the distinct metabolic profile of NK cells residing in the lungs opens new avenues for studying dysfunctional NK cells in respiratory diseases, suggesting that metabolism could be a target for immune-supportive therapies in respiratory diseases. conditions like cancer and chronic infections.

The researchers noted a surprising aspect of their findings: the willingness of cells residing in the lungs to activate their glycolytic pathways even before an infection occurs, almost as if they were primed and waiting for a sugar rush for them. enable. This metabolic preparation highlights a specialized adaptation of lung NK cells that makes them particularly effective in their local environment, which could be a key target for future treatments against lung diseases, including cancer and infections.

Lead author of the paper, Dr. Gráinne Jameson, describes her work: “These results are exciting because they establish that NK cells in the lungs are metabolically different from NK cells in the blood. dysfunctional NK cells in respiratory disease and shows that lung-resident NK cell metabolism is an actionable target for inhalable therapies for many lung disease settings, including cancer and infections.

Assistant Professor Sharee Basdeo from the Department of Clinical Medicine and lead author of the paper said: “This work used a state-of-the-art technique to establish the metabolic function of these NK cells collected from clinical lung washing samples. This allowed us to define for the first time how these cells that live in the lung use energy sources. These findings will enable future studies that support the function of lung-resident NK cells to better fight infections.