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Sökning: id:"swepub:oai:lup.lub.lu.se:3c2fcea9-8f97-4456-8724-e89f4e44e6c3" > Synovial monocytes ...

Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions

Schmidt, Tobias (författare)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Barnreumatologiskt forskningscentrum,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Center of Pediatric Rheumatology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine
Dahlberg, Alma (författare)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Pediatric Rheumatology Research Group,Forskargrupper vid Lunds universitet,Barnreumatologiskt forskningscentrum,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Center of Pediatric Rheumatology,WCMM-Wallenberg Centre for Molecular Medicine
Berthold, Elisabet (författare)
Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Barnreumatologiskt forskningscentrum,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Center of Pediatric Rheumatology,Lund University Research Groups
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Król, Petra (författare)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Barnreumatologiskt forskningscentrum,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Center of Pediatric Rheumatology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine
Arve-Butler, Sabine (författare)
Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,WCMM- Wallenberg center för molekylär medicinsk forskning,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,WCMM-Wallenberg Centre for Molecular Medicine
Rydén, Emilia (författare)
Lund University
Najibi, Seyed Morteza (författare)
Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
Mossberg, Anki (författare)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,WCMM-Wallenberg Centre for Molecular Medicine
Bengtsson, Anders A (författare)
Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
Kahn, Fredrik (författare)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neutrofiler – nya mekanismer och nya markörer,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Neutrophils – new mechanisms and new biomarkers,Lund University Research Groups
Månsson, Bengt (författare)
Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Pediatric Rheumatology Research Group,Forskargrupper vid Lunds universitet,Barnreumatologiskt forskningscentrum,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Center of Pediatric Rheumatology
Kahn, Robin (författare)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Pediatric Rheumatology Research Group,Forskargrupper vid Lunds universitet,Barnreumatologiskt forskningscentrum,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Center of Pediatric Rheumatology,WCMM-Wallenberg Centre for Molecular Medicine
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 (creator_code:org_t)
2023
2023
Engelska.
Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
Relaterad länk:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.3...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

Nyckelord

Humans
Arthritis, Juvenile
Interleukin-6/metabolism
Monocytes
Inflammation
Cytokines/metabolism
Cell Communication

Publikations- och innehållstyp

art (ämneskategori)
ref (ämneskategori)

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