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Synovial fluid potentiates local fibroblasts to drive monocyte activation in juvenile idiopathic arthritis

Schmidt, Tobias LU ; Mossberg, Anki LU ; Król, Petra LU ; Kapetanovic, Meliha C. LU ; Einarsson, Jon T. LU orcid ; Croft, Adam P. ; Bengtsson, Anders A. LU ; Kahn, Fredrik LU and Kahn, Robin LU (2026) In Arthritis Research and Therapy 28(1).
Abstract

Introduction: Synovial fibroblasts (S-Fib) are recognized as key drivers of joint inflammation in adult arthritis. Moreover, data are limited on the processes driving monocyte activation in oligoarticular juvenile idiopathic arthritis (oJIA). Therefore, we aimed to explore if S-Fib from patients with oJIA induce monocyte activation. Methods: S-Fib were isolated from the synovial fluid (SF) of n = 13 patients with oligoarticular juvenile idiopathic arthritis (oJIA) and n = 4 patients with rheumatoid arthritis (RA) to be used as a disease control. Healthy adult S-Fib were purchased. The interaction between monocytes and S-Fib was studied in co-cultures with monocytes isolated from healthy donors. These cells were analyzed by surface... (More)

Introduction: Synovial fibroblasts (S-Fib) are recognized as key drivers of joint inflammation in adult arthritis. Moreover, data are limited on the processes driving monocyte activation in oligoarticular juvenile idiopathic arthritis (oJIA). Therefore, we aimed to explore if S-Fib from patients with oJIA induce monocyte activation. Methods: S-Fib were isolated from the synovial fluid (SF) of n = 13 patients with oligoarticular juvenile idiopathic arthritis (oJIA) and n = 4 patients with rheumatoid arthritis (RA) to be used as a disease control. Healthy adult S-Fib were purchased. The interaction between monocytes and S-Fib was studied in co-cultures with monocytes isolated from healthy donors. These cells were analyzed by surface marker expression, cytokine production and T-cell activation. Moreover, S-Fib were “re-introduced” to the inflammatory synovial environment by priming or not with pooled cell-free SF from oJIA patients. The S-Fib were subsequently analyzed by cytokine production, ability to induce immune cell chemotaxis and mass spectrometry for proteomic changes, as well as their ability to induce monocyte activation as above. Results: Co-culture with S-Fib induced inflammatory activation of healthy monocytes as characterized by increased CD86 and HLA-DR expression, cytokine production and subsequent T-cell activation. Importantly, there were only minor differences in monocyte activation pattern depending on the source of the co-cultured S-Fib (oJIA, RA or healthy). Interestingly, compared to S-Fib alone, priming of S-Fib with a pool of SF induced an inflammatory phenotype, production of IL-6 and enhanced chemotaxis of monocytes. Additionally, primed S-Fib induced a more pronounced inflammatory phenotype in healthy monocytes compared to S-Fib alone. Finally, direct cell-cell contact between S-Fib and monocytes was required for full induction of the observed monocyte activation. Conclusions: Our data show a contact dependent role for S-Fib in driving inflammation in oJIA by inducing pro-inflammatory monocytes, processes potentiated by inflamed SF. These data further support that targeting cell-cell interactions could be a viable option to explore for novel treatment strategies in arthritis.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Inflammation, Juvenile idiopathic arthritis, Monocytes, Synovial fibroblasts, Synovial fluid
in
Arthritis Research and Therapy
volume
28
issue
1
article number
81
publisher
BioMed Central (BMC)
external identifiers
  • scopus:105035115855
  • pmid:41761349
ISSN
1478-6354
DOI
10.1186/s13075-026-03776-z
language
English
LU publication?
yes
id
27c7ca37-77e7-46e9-9190-351843f268a2
date added to LUP
2026-04-29 15:30:43
date last changed
2026-04-29 15:31:45
@article{27c7ca37-77e7-46e9-9190-351843f268a2,
  abstract     = {{<p>Introduction: Synovial fibroblasts (S-Fib) are recognized as key drivers of joint inflammation in adult arthritis. Moreover, data are limited on the processes driving monocyte activation in oligoarticular juvenile idiopathic arthritis (oJIA). Therefore, we aimed to explore if S-Fib from patients with oJIA induce monocyte activation. Methods: S-Fib were isolated from the synovial fluid (SF) of n = 13 patients with oligoarticular juvenile idiopathic arthritis (oJIA) and n = 4 patients with rheumatoid arthritis (RA) to be used as a disease control. Healthy adult S-Fib were purchased. The interaction between monocytes and S-Fib was studied in co-cultures with monocytes isolated from healthy donors. These cells were analyzed by surface marker expression, cytokine production and T-cell activation. Moreover, S-Fib were “re-introduced” to the inflammatory synovial environment by priming or not with pooled cell-free SF from oJIA patients. The S-Fib were subsequently analyzed by cytokine production, ability to induce immune cell chemotaxis and mass spectrometry for proteomic changes, as well as their ability to induce monocyte activation as above. Results: Co-culture with S-Fib induced inflammatory activation of healthy monocytes as characterized by increased CD86 and HLA-DR expression, cytokine production and subsequent T-cell activation. Importantly, there were only minor differences in monocyte activation pattern depending on the source of the co-cultured S-Fib (oJIA, RA or healthy). Interestingly, compared to S-Fib alone, priming of S-Fib with a pool of SF induced an inflammatory phenotype, production of IL-6 and enhanced chemotaxis of monocytes. Additionally, primed S-Fib induced a more pronounced inflammatory phenotype in healthy monocytes compared to S-Fib alone. Finally, direct cell-cell contact between S-Fib and monocytes was required for full induction of the observed monocyte activation. Conclusions: Our data show a contact dependent role for S-Fib in driving inflammation in oJIA by inducing pro-inflammatory monocytes, processes potentiated by inflamed SF. These data further support that targeting cell-cell interactions could be a viable option to explore for novel treatment strategies in arthritis.</p>}},
  author       = {{Schmidt, Tobias and Mossberg, Anki and Król, Petra and Kapetanovic, Meliha C. and Einarsson, Jon T. and Croft, Adam P. and Bengtsson, Anders A. and Kahn, Fredrik and Kahn, Robin}},
  issn         = {{1478-6354}},
  keywords     = {{Inflammation; Juvenile idiopathic arthritis; Monocytes; Synovial fibroblasts; Synovial fluid}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research and Therapy}},
  title        = {{Synovial fluid potentiates local fibroblasts to drive monocyte activation in juvenile idiopathic arthritis}},
  url          = {{http://dx.doi.org/10.1186/s13075-026-03776-z}},
  doi          = {{10.1186/s13075-026-03776-z}},
  volume       = {{28}},
  year         = {{2026}},
}