Sjögren’s syndrome is a chronic autoimmune disorder that affects millions worldwide, especially women, causing unrelenting dryness of the mouth and eyes. These symptoms severely impact daily life — making it hard to speak, eat, or sleep. Though doctors have long known the immune system targets the body’s own moisture-producing glands, the exact mechanism that shuts down saliva production remained a mystery. Scientists had clues that intercellular “zipper-like” structures were involved but lacked a clear picture of what failed, and how to fix it. The burning question lingered: What’s tearing open these cellular zippers — and can we seal them shut again?
On March 19, 2025, researchers at Peking University reported a series of pivotal findings that answer this very question. Their study (DOI: 10.1038/s41368-025-00349-9), published in the International Journal of Oral Science, revealed that tricellulin — a protein acting as a clasp at the three-way junctions of glandular cells — is destroyed early in the progression of Sjögren’s syndrome. Using human tissue samples and specialized mice, the team traced the damage to a specific inflammatory pathway. Most notably, they tested two intervention strategies: an investigational drug (AT1001) and a molecule that blocks microRNA-145. Both approaches successfully restored saliva secretion in mice, demonstrating that the damage is not only identifiable but also reversible.
The research showed that tricellulin functions as the glue at three-cell junctions in saliva glands. Its loss causes leakiness and disrupts normal secretion. Interferon-gamma and other inflammatory molecules launch a molecular cascade: they activate the JAK/STAT1 pathway, boosting levels of microRNA-145, which then targets and dismantles tricellulin. To confirm tricellulin’s central role, scientists engineered mice lacking the protein — and reproduced Sjögren’s symptoms almost exactly. The breakthrough came when they reversed this engineered damage: AT1001 repaired the cell junctions, while microRNA-145 inhibitors stopped the breakdown before it began. Both restored normal gland function, offering a potential blueprint for human treatment.
“This changes how we think about treating Sjögren’s syndrome,” said lead researcher Dr. Xin Cong. “We’re moving beyond simply calming inflammation — now we can fix the actual structural damage in the glands. It’s like repairing a burst pipe instead of just drying the floor. What’s even more encouraging is that both approaches worked, which gives us real confidence in developing patient-ready therapies.”
This discovery holds vast potential for the millions struggling with Sjögren’s dry mouth. Early detection of tricellulin loss could lead to preemptive care before irreversible damage sets in. The repurposing of AT1001, already tested for other illnesses, might accelerate clinical trials. Meanwhile, the microRNA-145 insight offers a gateway to highly targeted therapies that halt the problem at its root. Beyond Sjögren’s, this research could extend to other disorders involving damaged glands or leaky epithelial barriers — including dry eye disease and certain gut conditions. While clinical trials in humans are the next step, the leap from symptom management to glandular repair marks a watershed moment in autoimmune disease research.
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