Functional Analysis and Antigen Presentation in Striated Ductal Cells of Salivary Glands and Correlation With Sialoscintigraphy in Patients and Animal Models of Sjogren's Syndrome

Sjögren's syndrome is a complex autoimmune disorder characterized by CD4 T lymphocyte infiltration into the salivary glands, leading to impaired glandular function. The mechanisms underlying lymphocyte accumulation and activation in the absence of definitive antigen-presenting cells remain poorly understood. The investigators hypothesize that striated ductal cells, the primary target of lymphocyte invasion, may function as non-professional antigen-presenting cells in Sjögren's syndrome. However, there are currently no established methods to assess the functional status of striated ductal cells or their relationship with clinical presentations. To address this knowledge gap, the investigators aim to investigate the potential of sialoscintigraphy, a non-invasive imaging technique, to evaluate the functional status of striated ductal cells. The sodium iodide symporter (NIS), predominantly expressed in striated ductal cells, facilitates the transport of technetium-99m, a radiotracer used in sialoscintigraphy. The investigators hypothesize that the expression level of NIS, as evaluated through sialoscintigraphy, may serve as an indicator of striated ductal cell function and potentially correlate with clinical manifestations in Sjögren's syndrome. However, the literature and our preliminary data lead us to hypothesize that age and the specific major salivary gland being evaluated may introduce confounding factors in the interpretation of sialoscintigraphy results. Therefore, to address these hypotheses, our research proposal consists of three aims. First, establishing a nomogram of sialoscintigraphy stratified by age and specific salivary glands. The investigators will recruit healthy volunteers to receive sialoscintigraphy for the nomogram. This nomogram will provide a valuable reference for clinical application and further research in interpreting sialoscintigraphy results. Second, associating the expression level of NIS in the striated ductal cells from the major salivary glands with sialoscintigraphy, markers of antigen presentation, and disease manifestations of Sjögren's syndrome. The outcomes will help further applications of sialoscintigraphy in Sjögren's syndrome and formulate hypotheses to explore the pathological mechanisms underlying Sjögren's syndrome. Third, evaluating the capability of antigen presentation in striated ductal cells of salivary glands and to identify potential therapeutic targets. The investigators will examine their ability to uptake extracellular substances and validate their antigen-presenting ability using OT-II cells. Additionally, the investigators will perform RNA sequencing to identify potential therapeutic targets and manipulate their expression to evaluate their impact on the activation of OT-II cells. These findings will confirm that the striated ductal cells as non-professional antigen-presenting cells in Sjögren's syndrome and identify potential therapeutic genetic targets. Overall, our proposed research has the potential to utilize available diagnostic methods to evaluate the striated ductal cells, advance the understanding of how the non-professional antigen-presenting cells participate in the pathogenesis of Sjögren's syndrome, and contribute to the development of innovative therapies.