Characterization and Neutralization of Pathologic Memory CD4 +T Cells in Spondyloarthritis Synovial Fluid

Abstract

Abstract Spondyloarthritis (SpA), which has increased T helper 17 (Th17) cell activity, and neutralizing antibodies targeting IL-17 are effective in patients with SpA. However, not all Th17 cells are pathologic; most Th17 cells have physiological roles. Here, we characterize the immune landscape of blood and synovial cells in SpA through single cell to demonstrate the molecular characteristics of pathologic memory CD4 +T cells with Th17 characters. We identified pathologic Th17 (pTh17) cells as polyfunctional IL-17A and IFN-γ-producing memory CD4 +T cells, with clinically supporting evidence for their pathogenic roles at the inflammatory site of SpA. Transcriptome and flow cytometric analysis found that the co-expression of TNFRSF4 and TNFRSF18 is increased in pTh17 cells. Suppression of ligand-receptor interactions via TNFRSF4 and TNFRSF18 effectively decreased clinical arthritis and decreased pTh17 cells in the curdlan-injected SKG mouse model. Our results provide understanding pTh17 cells in SpA and suggest potential therapeutic targets.