Interleukin-17 (IL-17) is a key inflammatory protein that drives joint inflammation in spondyloarthritis (SpA), a chronic immune-mediated condition affecting the spine and other joints. Until recently, the exact cellular source of IL-17 in inflamed joints remained unclear.
A new study published in Annals of the Rheumatic Diseases reveals that CD4+ tissue-resident memory Th17 (TRM17) cells are the primary producers of IL-17 in the synovial tissue of SpA patients. Unlike circulating CD4+ Th17 cells, these TRM17 cells remain within joint tissue, continuously producing IL-17 and sustaining local inflammation.
‘This is a significant step forward in our understanding of SpA,’ said Dr. Liye Chen, Versus Arthritis Career Development Fellow at NDORMS, University of Oxford, and senior author of the study. ‘We’ve identified CD4+ TRM17 cells as the main source of IL-17 in SpA joints—a previously unrecognised role.’
The research team applied single-cell RNA sequencing and spatial transcriptomics to analyse synovial tissue from patients with axial SpA and psoriatic arthritis. Their findings challenge previous assumptions by showing that CD4+ TRM17 cells—not gamma delta (γδ) T cells or innate lymphoid cells—are the dominant IL-17 producers in the inflamed joint environment.