TCR repertoire analysis reveals effector memory T cells differentiation into Th17 cells in rheumatoid arthritis

The pathogenesisof rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor(TCR) repertoiresof different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naive RA patients and healthy controls were sorted into seven subsets including naive, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptorbeta chain repertoireswere then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoiresbetween them. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively correlated with RA disease activity indices such as C-reactive protein and erythrocyte sedimentation rate. Thus, shared and abnormally expanded EMT and Th17 TCR repertoiresmight be pivotal for RA pathogenesis.