GZMK+ CD8+ T Cells Drive Selective Acinar Cell Loss and Interferon Signaling in Sjögren’s Disease

Highlight

– Single-cell and spatial transcriptomics identify a previously unrecognized PRR4⁺CST3⁺WFDC2⁻ seromucous acinar population that is selectively depleted in Sjögren’s disease (SjD).
– GZMK⁺CD8⁺ T cells accumulate with disease severity, show a cytotoxic yet sub-lytic program, and spatially co-localize with immune-engaged epithelial cells.
– Functional assays indicate GZMK impairs mitochondrial integrity and triggers interferon signaling in epithelial cells — linking targeted epithelial injury to type I interferon responses and suggesting new therapeutic targets.

Background: clinical context and unmet need