First data in RA - Cytodata 2025

At CytoData 2025 in Berlin, we presented first data from our rheumatoid arthritis (RA) program, linking the activation of CD4+ T cells by RA joint fluid to cell migration.

In blood immune cells (PBMCs) exposed to joint (synovial) fluid, we identified activated CD4+ T cells by high-content imaging. Fluid from RA patients activated them most, fluid from osteoarthritis patients less and fluid from healthy donors least, and the RA drug baricitinib reduced this activation. Fluid-exposed T cells shifted toward the activated, effector and proliferating T cell states of a published RA synovial tissue atlas.

To find modulators of this activation, we started from an earlier screen of 587 compounds and other agents in healthy donor PBMCs and used a protein–protein interaction network to predict further modulators. Tested in PBMCs primed with RA synovial fluid, the predicted modulators had a higher hit rate than the original screen. The hits’ targets were enriched for migration pathways, and synovial fluid upregulated migration and activation pathways in CD4+ T cells. In a transwell assay, activated T cells migrated preferentially, and RA synovial fluid amplified their migration.