Sjögren’s syndrome is a chronic autoimmune disease that affects millions of people worldwide, especially women, causing dry and uncomfortable mouth and eyes. These symptoms seriously affect daily life, which makes it difficult to speak, eat or sleep. Although doctors have long known that the immune system targets the body’s own glands that produce water themselves, the exact mechanism that turns off saliva production remains a mystery. Scientists have clues that can involve intercellular “zipper” structures, but lack clear circumstances, namely failure and how to fix it. The burning problem lingers: What is the tear on opening these honeycomb zippers – can we seal them again?
On March 19, 2025, researchers at Peking University reported a series of key findings that answered the question. Their study (doi: 10.1038/s41368-025-00349-9) was published in International Journal of Oral SciencesIt is revealed that in the early stages of sjögren syndrome, trichondrogen protein (a protein that acts at the tridirectional junction of gland cells) is destroyed. The team used human tissue samples and specialized mice to trace the damage back to specific inflammatory pathways. Most notably, they tested two intervention strategies: a study drug (AT1001) and a molecule that blocks microRNA-145. Both methods successfully restored saliva secretion in mice, indicating that the damage is not only recognizable, but also reversible.
This study shows that trichondrin acts at the joints of three cells in the salivary glands. Its loss can cause leakage and destroy normal secretion. Interferon-gamma and other inflammatory molecules trigger molecular cascades: They activate the JAK/STAT1 pathway, enhance the levels of MicroRNA-145, and then target and remove trifibrin. To confirm the central role of trifibrin, scientists designed mice that lack protein and reproduced Sjögren’s symptoms almost accurately. The breakthrough came as they reversed this engineering damage: AT1001 repaired the cellular junction, while MicroRNA-145 inhibitor stopped malfunctioning before it started. Both restore normal glandular function, providing a potential blueprint for human treatment.
“This has changed our perception of treating Sjögren syndrome,” said lead investigator Dr Xin Cong. “We have gone beyond simple inflammation – now we can repair actual structural damage in the glands. It’s like repairing burst pipes, not just drying the floor. More encouraging, both methods work, which gives us real confidence in developing patient-ready therapies.”
This discovery has great potential, the struggle of millions of sjögren’s dry mouth. Early detection of tricellulose loss may lead to preemptive care before irreversible damage. Reuse of the reuse of AT1001, which has been tested for other diseases, may speed up clinical trials. Meanwhile, MicroRNA-145 Insight provides a portal to highly targeted therapies that block the root cause of the problem. In addition to Sjögren’s, the study could also be extended to other diseases involving damaged glands or leaking epithelial barriers, including dry eye and certain intestinal diseases. Although clinical trials in humans are the next step, the leap from symptom management to gland repair marks a watershed moment in autoimmune disease research.
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