A large-scale analysis by La Jolla Institute for Immunology scientists has identified genetic factors in lung immune cells that may contribute to the development of autoimmune diseases, according to an Aug. 3 report.
The research team analyzed more than 1.1 million tissue-resident immune cells from the lungs of 128 human volunteers. These cells, which remain in the lungs rather than circulating in the blood, play a key role in defending against respiratory infections and diseases such as lung cancer. However, some tissue-resident immune cells can become dysfunctional and cause inflammation, particularly in patients with autoimmune conditions like lupus, rheumatoid arthritis, or scleroderma.
The study found that certain genes expressed by these lung immune cells are associated with genetic risk factors linked to both lung and autoimmune diseases. "This is a foundational paper for any researcher asking whether genetics has a role in an autoimmune disease," said Pandurangan Vijayanand, M.D., Ph.D., William K. Bowes Distinguished Professor at LJI.
Researchers used healthy sections of lung tissue donated by patients newly diagnosed with lung cancer who were undergoing surgery. The samples and clinical data were collected through the Target Lung study led by University of Liverpool Professor Christians Ottensmeier, MD, Ph.D. This project was part of the Database of Immune Cell Epigenomics (DICE), which aims to connect genetic variations with immune cell function.
Using single-cell RNA sequencing technology, LJI researchers identified around 1,000 genes impacted specifically by genetic factors within tissue-resident immune cells—differences not seen in blood-based immune cells. The analysis also revealed sex-based differences: approximately 1,700 genes showed different expression levels between male and female participants and may be important for infectious or autoimmune disease development.
The scientists say further research is needed to fully understand how these unique characteristics of tissue-resident immune cells influence disease progression in the lungs. "DICE is a rich resource," Vijayanand said.
