Chronic inflammation of the lacrimal and salivary glands is a common feature of aging and autoimmune diseases such as Sjögren’s syndrome (SS), which affects significant number of people within the US population. Despite the existence of several biological therapies currently in clinical trials, there is no effective therapeutic treatment available for SS and aging patients. Furthermore, the development of disease-modifying drugs requires a better understanding of the cellular responses to chronic inflammation, which is an area that has not been extensively studied.

     Our study focuses on investigating the molecular and cellular mechanisms underlying lacrimal gland inflammation. Our research has shown that acinar and myoepithelial cells are critical players in the development of lacrimal and submandibular gland dysfunction during inflammation and aging, and that the stimulation of myoepithelial cells may improve the function of secretory cells. Using RNA-seq and Visium spatial transcriptomics analyses, we have found that in NOD mice, genes involved in peroxisome proliferator-activated receptor α (PPAR-α) signaling and fatty acid metabolism are downregulated, while enzymes involved in cholesterol biosynthesis are upregulated. This suggests that altered lipid metabolism in the lacrimal gland is likely to trigger epithelial cell damage, leading to sustained inflammasome activation and immune cell priming.

     Additionally, we have evidence that ATP-releasing channels, such as pannexins, and inflammasome formation may have both "protective" and "harmful" functions in the development of inflammation. We believe that therapeutic modulation of Panx1 channels, inflammasome pathways, and/or lipid pathways represents a promising new strategy for reducing inflammation and promoting regeneration.