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- Schmidt, Tobias, et al.
(author)
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Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions
- 2023
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In: Frontiers in Immunology. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment.METHODS: The function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems.RESULTS: Synovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. In vitro, synovial fluid from patients induced the regulatory features in healthy monocytes, such as resistance to cytokine production and increased efferocytosis. IL-6/JAK/STAT signalling was identified as the main pathway induced by synovial fluid, which also was responsible for a majority of the induced features. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels, reflecting two groups of low vs. high local and systemic inflammation. Remaining features, such as an increased ability to induce T-cell activation and markers of antigen presentation, could be induced by cell-cell interactions, specifically via co-culture with fibroblast-like synoviocytes. CONCLUSIONS: Synovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g., via promoting adaptive immune responses. 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.
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2. |
- Wallner, Lars, 1983-, et al.
(author)
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Students’ Constructions of Professional Judgement in Teacher Education, Medical Education and Police Education
- 2024
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In: Högre Utbildning. - 2000-7558. ; 14:1, s. 49-63
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Journal article (peer-reviewed)abstract
- Vocational training programmes in higher education encompass, as learning objectives, the development of relational skills and professional judgement, especially in welfare professions such as policing, teaching and healthcare, where know-how about managing close contact with people is a prerequisite. Based on a cross-professional analysis, the current article explores how students from three different professional education programmes – teacher education, police training and medical education – construct professional judgement in group discussions and interviews. The results show that participants construct professional judgement as relationships between three different dimensions: personal ethics, educational standards, and professional practice. When discussing professional dilemmas, students utilise these three different dimensions to argue for the moral or ethical soundness of their choices. The results of the study shed light on the importance of providing students with opportunities to reflect openly on professional judgement in different ways, even though such reflections may not always be formally assessed. Furthermore, the analysis demonstrates similarities between the three programmes that we analysed, as well as similarities in students’ reflections regarding essential aspects of the professions.
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