Key Findings
Researchers led by Assistant Professor Masaru Takeshita at Keio University School of Medicine identified CD4+ T cells that recognize the Ro60 protein in salivary glands of Sjögren's disease patients.
The study combined single-cell RNA sequencing with T-cell receptor (TCR) analysis to identify over 200 TCRs from infiltrating immune cells. Using engineered reporter cells and artificial antigen-presenting systems, 13 TCRs were confirmed to specifically recognize Ro60-derived peptides.
Many Ro60-reactive T cells belonged to T follicular helper subsets that stimulate antibody-producing B cells. Anti-Ro60 antibodies bind to Ro60 proteins from damaged cells, forming immune complexes that are taken up by antigen-presenting cells, which present Ro60 peptides to CD4+ T cells, activating them and promoting further antibody production—a self-reinforcing loop.
Results were consistent across Japanese and Caucasian patients, suggesting a general mechanism in anti-Ro60-positive Sjögren's disease.
Implications
The findings may enable development of therapies that selectively interrupt the pathogenic loop without broadly suppressing the immune system.
The study was published online in Science Advances on June 3, 2026 (DOI: 10.1126/sciadv.aeb2491).