Investigating age-related immune dysfunction in lung epithelial cells

The Jackson Laboratory's Karolina Palucka speaking at the American Cancer Society Cancer Action Network CT Forum in Farmington, December 1, 2022 at JAX. Photo by Cloe Poisson.

With $13 million in renewed support, Karolina Palucka, M.D., Ph.D., will further study how aging affects airway epithelial cells' efficiency in combating viral infections, with the potential for identifying new targets for preventative interventions in older populations.

Investigating the lungs' first line of defense

Covering the surface of the respiratory tract, airway epithelial cells protect the lungs from potentially harmful inhaled substances, including respiratory viruses such as influenza and SARS-CoV-2. As seen each flu season and globally during the COVID-19 pandemic, individuals over the age of 65 are particularly susceptible to viral infections. While it is apparent that the innate and adaptive immune systems in the aging population change over time, exactly what occurs, especially in lung-tissue-residing immune cells, is not well understood. As the first site where respiratory viruses infect and replicate, it is critical to understand more about how airway epithelial cells operate and affect other cells in the lung environment.

Professor and Director of The Jackson Laboratory's NCI-designated basic research Cancer Center, Karolina Palucka, M.D., Ph.D., specializes in human immunology. Initially supported by an $11 million National Institute of Allergy and Infectious Diseases grant within the Cooperative Centers on Human Immunology program in 2019, Paluckaled a multidisciplinary team in investigating how airway epithelial cells and the lung microbiome play a role in the immune response to viral infection. Now, with $13 million in renewed support,she and her colleagues will explore antiviral responses and age-related changes in lung epithelial cells.

The researchers will utilize air-liquid-interface (ALI) cultures to study how airway epithelial cells respond to pathogenic viruses, as well as what cross-talk occurs between other host immune cells and lung-residing microbes when combating infection. Using ALI cultures will allow the team to analyze the specific genes, pathways, transcriptional responses, epigenetic factors and RNA modifications driving the molecular mechanisms of both normal immune responses and the changes that occur in the lung epithelial cells of older adults. This work will potentially identify new targets or approaches to prevent severe viral infections. Furthermore, by elucidating the mechanisms driving aging-associated inflammation, Palucka's findings might provide further insights into the biology of lung cancer.