Spatial transcriptomic profiling identifies lacrimal-gland-epithelial cell-driven mechanisms underlying autoimmunity in Sjögren’s disease

This finding supports the potential use of tear sIgA as a quantifiable biomarker of glandular dysfunction. By integrating spatial and cellular information, we uncovered a previously unrecognized spatial relationship between ductal epithelial cells and antigen-presenting cells in the lacrimal gland and identified a potential role for ductal epithelial cells as active drivers of inflammation by providing molecular and cellular cues that support periductal infiltrates rich in B cells and T follicular helper cells that form germinal centers and promote local autoantibody production. These findings together generate testable mechanistic hypotheses for each epithelial subtype and propose a framework for the therapeutic targeting of epithelial cells and multicellular interactions that underlie autoimmune lacrimal gland pathology in SjD.