Researchers have identified a possible cause for the protein Interleukin-17 (IL-17) driving inflammatory arthritis, paving the way for the development of targeted therapies to treat the condition.
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 and supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC), 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 the 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.
Prof Holm Uhlig of the Oxford-J&J Cartography Collaboration and Oxford BRC Co-theme Lead for Inflammation Across Tissues, said: “We’re delighted to see the contribution of the Cartography Collaboration to this important discovery. This study shows the transformative power of single-cell and spatial transcriptomics in uncovering the cellular drivers of immune diseases like spondyloarthritis and guiding effective, precision therapies.
“With detailed maps of over 4.5 million cells from across inflammatory conditions, Cartography will continue to fuel new insights and innovative treatments like this.”
Dr Chen added: “Current IL-17-blocking therapies benefit about half of SpA patients but require ongoing treatment and rarely lead to lasting remission. By targeting the CD4+ TRM17 cells themselves—the ‘factories’ of IL-17—we may be able to achieve long-term control of inflammation without continuous medication.”
As well as the Oxford BRC, this study was funded by Versus Arthritis, and Johnson & Johnson Innovative Medicine through support for the Cartography Consortium.