NYC Gazette

Researchers at NYU College of Dentistry and NYU Grossman School of Medicine have made progress in understanding Sjögren’s disease, an autoimmune disorder. Their study highlights the role of calcium signaling, regulatory T cells, and interferon in the disease's development.

The findings, published in Science Translational Medicine, reveal that impaired regulatory T cells significantly contribute to Sjögren’s disease in both mice and humans. The study also identifies a rheumatology drug as a potential therapy for the condition.

Sjögren’s disease causes the immune system to attack glands producing saliva and tears, leading to dry mouth and eyes. It can also affect other body parts, causing fatigue, joint pain, rashes, and lung inflammation.

“Not being able to produce tears or saliva can have a great impact on one’s life,” said Rodrigo Lacruz from NYU College of Dentistry. He noted that lack of saliva could impair speech and increase cavity risk.

A key aspect of Sjögren’s disease diagnosis is autoantibodies in blood and lymphocytes in salivary glands. While there is no cure, some treatments alleviate symptoms but do not provide complete relief.

“Sjögren’s disease is an inflammation-driven disease,” stated Stefan Feske from NYU Grossman School of Medicine. Existing therapies deplete B cells with antibodies but have shown mixed results in trials.

Feske and Lacruz conducted studies on salivary gland cells and immune cells to understand cellular contributions to Sjögren’s disease. They focused on cells lacking Stim1 and Stim2 genes, which disrupt calcium signaling.

Calcium signaling is crucial for saliva production but its role in Sjögren’s development was unclear. Research published in Function studied mice without Stim1 and Stim2 genes in salivary gland cells. These mice showed reduced saliva production due to low calcium levels but did not develop inflammation typical of human Sjögren’s disease.

“We found that a specialized calcium channel activated by STIM1 and STIM2 proteins is essential for driving saliva secretion,” said Lacruz.

Previous research showed that altering mice genetically to lack calcium signaling led to dysfunction in regulatory T cells, prompting inflammation. These findings were further explored by Feske focusing on regulatory T cells rather than salivary gland cells.

Mice with dysfunctional regulatory T cells exhibited severe inflammation similar to Sjögren’s symptoms: dry eyes, dry mouth, autoantibodies, and lymphocytes in salivary glands. Some developed lung inflammation as well.

“Knocking out these two genes drove a cascade of immune dysfunction,” Feske explained. Further analysis concluded that dysfunction of regulatory T cells could occur through various pathways beyond calcium signaling.

A likely cause for symptoms was identified as interferon gamma overactivation due to defective regulatory T cells failing to inhibit other immune responses effectively.

“It came down to a defect in regulatory T cells," said Feske about interferon gamma's critical role in causing gland dysfunctions seen in their mouse model studies.

Researchers tested baricitinib—a JAK inhibitor used for rheumatoid arthritis—finding it suppressed gland dysfunction when administered to mice with Sjögren-like symptoms suggesting potential therapeutic application against this autoimmune disorder going forward according Dr.Feske's assessment based upon correlation between genetic signatures observed across both human patient samples alongside experimental models involving murine subjects under controlled conditions .

Authors involved include Yin-Hu Wang ,Wenyi Li ,Maxwell McDermott,Fang Zhou among others affiliated either directly via respective institutions namely:NYU Grossman School Medical/College Dentistry University Rochester along collaborators international partnerships including China's Central South University/NYU Abu Dhabi backed financially National Institutes Health alongside regional initiatives aimed fostering innovation academic excellence within scientific community globally oriented towards addressing pressing challenges confronting modern medicine today particularly concerning autoimmune diseases such complex multifactorial origins demanding comprehensive approaches integrate cutting-edge technologies methodologies spanning diverse disciplines ensure effective solutions ultimately benefit patients worldwide impacted disorders like sjogrens characterized chronic debilitating nature necessitating continued efforts advance knowledge therapeutic options available clinicians managing care delivery systems effectively meet needs those affected populations requiring assistance maintain quality life despite limitations imposed illness itself