Objectives Synovial monocytes in oligoarticular juvenile idiopathic arthritis (oJIA) are polarized, but little is known of how they contribute to disease and attain their pathogenic features. The aim of this study was to investigate the role of monocytes in the pathogenesis of oJIA. Methods The function of synovial monocytes was analysed by several assays believed to reflect key pathogenic events, such as T-cell activation-, efferocytosis- and cytokine production assays through flow cytometry in untreated oJIA patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry, broad-spectrum phosphorylation assays and functional assays. Additional effects on monocytes were studied through co-cultures with primary fibroblast-like synoviocytes. Results The results demonstrate that synovial monocytes display functional alterations, e.g., increased ability to induce T-cell activation, increased efferocytosis and resistance to cytokine production following activation with LPS. In vitro, synovial fluid induced regulatory features in healthy monocytes through an IL-6/JAK/STAT mechanism. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels. An increased ability to induce T-cell activation and markers of antigen presentation could be induced by co-culture with fibroblast-like synoviocytes. Conclusions Synovial monocytes in oJIA are functionally affected, drive chronic inflammation, and promote adaptive immune responses. This phenotype can be replicated in vitro through a combination of synovial fluid (through IL-6/JAK/STAT) and cell-cell interactions. These data support a role of monocytes in the pathogenesis of oJIA and highlight a group of patients more likely to benefit from targeting the IL-6/JAK/STAT axis to restore synovial homeostasis.

The authors have declared no competing interest.

RK is funded by grants from the Swedish League against Rheumatism, Greta and Johan Kocks Foundation, the Anna-Greta Crafoord Foundation, the Crafoord Foundation, Alfred Osterlunds Foundation, Magnus Bergvall Foundation, King Gustaf Vs 80-year foundation, The Knut and Alice Wallenberg foundation, the Medical Faculty at Lund University and Region Skane. The funders had no role in the concept, design, or interpretation of data.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Regional Ethical Review Board for southern Sweden (2016/128) gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors. The raw proteome data is available via ProteomeXchange with identifier PXD033983.

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