ANTIGEN-PRESENTING CELLS AND INTERFERONS IN RHEUMATOID AND JUVENILE IDIOPATHIC ARTHRITIS

Abstract

Rheumatoid (RA) and juvenile idiopathic arthritis (JIA) are heterogeneous chronic inflammatory diseases with incompletely understood pathogenesis. The study of antigen-presenting cells may provide insights into the pathophysiology. Hypothesis: The imbalance in novel type I and III interferons (IFN) produced by dendritic cells (DC), as well as the naturally occurring tolerogenic profile of DCs, could help identify individuals with varying clinical symptoms or therapeutic responses. Results: Type I IFNκ was strongly and selectively expressed in JIA, with differences among JIA subtypes. Conventional DCs (cDCs) showed an altered tolerogenic profile associated with increased IFNγ and IFNλ1 expression in synovial fluid (SF). In RA, the disease activity (DA) improvement after methotrexate treatment was associated with the baseline expression of IFNλ1, primarily produced by the CD141+cDC1s. Interestingly, the cDC1s, which are infrequent in the periphery, significantly accumulate in the SF. Conclusion: cDC1s play a key role in pathogenesis and contribute to disparities in therapy-response.