A research team at the Keio University School of Medicine's Division of Rheumatology has revealed at a single-cell level that the immune response and inflammation mechanisms in the salivary glands of patients with the autoimmune disorder Sjögren's disease differ according to the type of autoantibodies. The Keio team includes Jun Inamo (co-first author), Masaru Takeshita (co-first author), Yuko Kaneko, and Tsutomu Takeuchi, in collaboration with Immune-mediated Inflammatory Diseases Consortium for Drug Development—an industry–academia collaborative research organization led by Keio University School of Medicine—and the Laboratory for Regulatory Genomics (Team Director: Chung-Chau Hon) at the RIKEN Center for Integrative Medical Sciences (IMS).
This study employed an integrative approach combining cutting-edge methods, including single-cell analysis to comprehensively profile gene expression in individual salivary gland cells and spatial transcriptome analysis to assess cells in their tissue context. The results revealed three key findings: (1) expansion of cytotoxic GZMB+GNLY+CD8 positive T cells that directly attack the salivary glands, (2) distinct inflammatory pathways associated with different autoantibody types, and (3) THY1 positive fibroblasts functioning as a local "command center" orchestrating inflammation. These insights mark an important step toward developing fundamental treatments for Sjögren's disease, which until now has been managed primarily with symptomatic therapies, paving the way for therapies targeting both common and distinct disease pathways, tailored to each patient’s specific condition.
These research findings were published in the international scientific journal Nature Communications on September 22, 2025 (London time).
