Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in childhood, affecting 1 in 10,000 children. Despite advances in therapy, a significant proportion of children experience chronic and relapsing disease courses. Natural killer (NK) cells constitute 10–40% of the total lymphocyte population, yet their roles in JIA remain poorly characterized.

To profile synovial NK cells in JIA, we obtained paired blood and synovial fluid samples from six patients and performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis. We found that the majority of synovial NK cells belong to the CD56^bright subset and exhibit features of tissue residency, including expression of CD49a, CD103, CD69, and the transcription factor HOBIT. We assessed cytokine production by these cells and identified NK cells as major producers of GM-CSF within the inflammatory synovium, a cytokine strongly implicated in the pathology of inflammatory arthritis.

These data highlight novel roles for NK cells in the pathogenesis of pediatric arthritis, providing insights that may inform future therapeutic strategies.