Cystic fibrosis is a disease caused by inherited genetic mutations that disrupt or entirely stop the production of the CFTR protein. This condition primarily impacts the respiratory system, where mucus becomes so thick that it prevents pathogens like bacteria from being expelled through coughing, leading to a dangerous cycle of infection and inflammation.
To mitigate these effects, medical professionals have increasingly turned to CFTR modulator therapies in recent years. These treatments enhance the protein’s function, reducing mucus production and significantly improving the quality of life for those affected. Despite these advancements, clinical studies indicate that airway inflammation is still common, and in older patients, the deterioration of lung function continues unabated.
Ongoing research is dedicated to uncovering further processes involved in cystic fibrosis. Professor Nikolai Klymiuk from the Technical University of Munich, part of an international research team, has focused on how the immune system behaves in cystic fibrosis before the cycle of infection and inflammation begins. Their findings, published in Science Translational Medicine, reveal significant insights into the immune response associated with the disease.
The research team found that specific innate immune system cells in blood samples from children with cystic fibrosis and pigs with the same genetic defect are immature. This immaturity makes them less effective at fighting off bacteria. Additionally, pigs with cystic fibrosis also showed an increased number and significantly altered composition of immune cells in their lungs from birth. Given the strong resemblance between the immune systems of pigs and humans, these observations are likely applicable to human patients as well.
The researchers propose that these changes in the immune system may result from an “emergency program,” which prompts the body to produce many immune cells quickly and over a prolonged period. This leads to the formation of immature immune cells, which contribute to the fatal cycle of infections and inflammation characteristic of cystic fibrosis. Although these cells are present in the lungs, they are ineffective and damage lung tissue without preventing infections over the long term.
Professor Klymiuk, who specializes in Cardiovascular Translation in Large Animal Models at TUM, notes that while it remains unclear why such changes in immune cells occur, they are evident early in life and persist throughout the individual’s lifetime. Previously thought to result from frequent infections in adults, these altered immune cells are now understood to be a fundamental aspect of the disease from its onset. Professor Klymiuk believes that to enable people with cystic fibrosis to live without symptoms, a comprehensive approach to treating the disease is necessary. He hopes that the insights from their research will lead to a better understanding of the defective immune system and inform future treatment strategies.
More information: Nikolai Klymiuk et al, Perinatal dysfunction of innate immunity in cystic fibrosis, Science Translational Medicine. DOI: 10.1126/scitranslmed.adk9145
Journal information: Science Translational Medicine Provided by Technical University of Munich (TUM)
