Study identifies key immune cell changes in the lungs of people with sarcoidosis

Researchers at National Jewish Health and partner institutions discovered specific changes in immune cells in the lungs of people with sarcoidosis. Their findings help explain how this inflammatory disease develops and could support the development of new treatments in the future.

The study, published in Frontiers in Immunology, used advanced single-cell RNA sequencing technology to examine individual immune cells collected from the lungs of patients with pulmonary sarcoidosis. By analyzing cells one at a time, researchers were able to identify molecular differences that may be hidden when studying large groups of cells together.

Sarcoidosis is an inflammatory disease that can affect multiple organs but most commonly involves the lungs. The disease causes clusters of immune cells, known as granulomas, to form in affected tissues. While many patients experience mild disease, others develop progressive lung damage that can significantly impact breathing and quality of life.

Our findings provide a more detailed picture of the immune cells involved in pulmonary sarcoidosis and how those cells communicate with one another. Understanding these cellular interactions may help identify new targets for future therapies and improve our understanding of why the disease behaves differently from one patient to another."

Lisa A. Maier, MD, co-senior author of the study, pulmonologist and researcher, National Jewish Health

The research team analyzed lung immune cells from 16 patients with sarcoidosis and 14 healthy volunteers. They identified disease-associated patterns of gene activity in macrophages, a type of immune cell that plays a key role in inflammation and granuloma formation. The researchers also observed fewer B cells in patients with the disease and heightened inflammatory activity in CD4-positive T cells, which play a central role in directing immune responses.

The study further revealed changes in how immune cells communicate with one another inside the lung. While overall communication between immune cells appeared reduced in patients with sarcoidosis, interactions involving CD4-positive T cells were relatively increased, suggesting a shift in immune system behavior that may contribute to disease development and progression.

These findings provide new insight into the cellular mechanisms underlying pulmonary sarcoidosis and may help researchers identify future targets for more precise therapies.

"Our findings highlight the complexity of immune dysregulation in sarcoidosis and deepen our understanding of the processes that may contribute to disease," said Camille Moore, PhD, first author on the study and a researcher at National Jewish Health. "We hope this work will help guide future research aimed at improving the diagnosis and treatment of sarcoidosis."

The researchers noted that while additional studies are needed, the findings help build a more comprehensive understanding of the biological mechanisms underlying pulmonary sarcoidosis and may guide future efforts to develop more targeted therapies.