#2-44E. Targeting Specific Acinar Cells: The Sub-Cytolytic Mechanism of GZMK+CD8+ T Cells in Sjögren’s Disease (ARD, 2025)

Why do we still lack effective therapies that prevent the glandular dysfunction characteristic of Sjögren’s Disease (SjD)? This landmark study utilized single-cell and spatial transcriptomics to dissect the complex cellular pathology in SjD salivary glands, revealing previously unrecognized acinar cell heterogeneity. The investigation identified a selective loss of the PRR4+CST3+WFDC2⁻ seromucous acinar population in SjD patients, linking this specific epithelial vulnerability to the severity of immune infiltration. The most critical finding focuses on the accumulating GZMK+CD8+ T cells, which drive tissue damage through a novel sub-cytolytic effector mechanism. These cells disrupt mitochondrial integrity in target epithelial cells and activate innate immune signaling, thereby providing a mechanistic link to the characteristic Type I IFN signature observed in SjD. While this work identifies GZMK+CD8+ T cells and their unique pathway as a crucial axis of pathogenesis, we must remember that real-time, direct observation of these sub-cytolytic events in situ has not yet been possible. This insight is vital for clinicians, as it identifies a novel cellular and mechanistic target, offering a pathway for developing disease-modifying agents that specifically mitigate tissue damage.

Citation: Pranzatelli TJF, Perez P, et al. GZMK+CD8+ T cells target a specific acinar cell type in Sjögren’s disease. Annals of the Rheumatic Diseases. 2025.

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.