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Lung immune cells may drive autoimmune disease, study finds
The Nature Immunology study also found sex-based genetic differences that may explain higher autoimmune risk in women.
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Pranavi Sharma - Tue, 04, Aug 2026
- 03:04 EDT
- 20
Study senior author Pandurangan Vijayanand, M.D., Ph.D., LJI William K. Bowes Distinguished Professor / La Jolla Institute
Scientists at the La Jolla Institute for Immunology have identified specialized immune cells in human lung tissue that may contribute to the development of autoimmune diseases, according to a new study led by Indian American researcher Pandurangan Vijayanand and published in Nature Immunology. The findings are based on an analysis of more than 1.1 million immune cells from the lungs of 128 study volunteers.
The researchers examined "tissue-resident" immune cells, which remain in the lungs and help protect the body against respiratory infections, disease and lung cancer. Their analysis found that these cells express genes associated with the risk of autoimmune and lung diseases, suggesting they may play a direct role in disease development rather than simply responding to inflammation.
The findings may help explain why some people develop autoimmune conditions such as rheumatoid arthritis, lupus and scleroderma, all of which can involve chronic lung inflammation.
The research team analyzed healthy sections of lung tissue donated by 128 patients who had recently been diagnosed with lung cancer and were undergoing surgery. The tissue samples and clinical data came from participants in the Target Lung study, led by Professor Christians Ottensmeier of the University of Liverpool.
The work was conducted as part of the Database of Immune Cell Epigenomics, or DICE, project, which investigates how genetic variation influences immune cell function and disease susceptibility.
Using single-cell RNA sequencing, the researchers studied gene expression in individual tissue-resident immune cells to understand how genetic factors influence their behavior.
"We analyzed thousands of immune cells from lung tissue for each study volunteer," said Benjamin Schmiedel, an assistant professor at the La Jolla Institute for Immunology. "No study has produced and analyzed a dataset at this scale and resolution before."
According to the researchers, the analysis identified about 1,000 genes influenced by genetic factors that were found specifically in tissue-resident immune cells but not in immune cells circulating in the blood.
The study also found significant differences between male and female participants. Researchers identified 1,700 genes with sex-based differences in expression, several of which are involved in inflammatory pathways linked to infectious and autoimmune diseases.
Many of those genes showed higher expression in one sex than the other, a finding the researchers said may help explain why autoimmune diseases are generally more common in women.
"This is a foundational paper for any researcher asking whether genetics has a role in an autoimmune disease," said Vijayanand, the study's senior author and the La Jolla Institute's 'William K. Bowes Distinguished Professor'.
The researchers said additional studies are needed to better understand how tissue-resident immune cells contribute to disease in the lungs. Vijayanand said the DICE project provides scientists with a valuable resource for studying immune cell function across people of different ages, sexes and genetic backgrounds.
"DICE is a rich resource," he said.
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