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Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment - a distinct inflammatory pattern for oligoarticular juvenile arthritis

Schmidt, Tobias LU ; Berthold, Elisabet LU ; Arve-Butler, Sabine LU orcid ; Gullstrand, Birgitta LU ; Mossberg, Anki LU ; Kahn, Fredrik LU ; Bengtsson, Anders LU ; Månsson, Bengt LU orcid and Kahn, Robin LU (2020) In Arthritis Research & Therapy 22.
Abstract
Background
Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).

Methods
Paired synovial fluid, blood samples (n = 13), and synovial biopsies... (More)
Background
Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).

Methods
Paired synovial fluid, blood samples (n = 13), and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization, and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence, and in situ hybridization.

Results
Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001), and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies.

Conclusion
Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research & Therapy
volume
22
article number
186
publisher
BioMed Central (BMC)
external identifiers
  • pmid:32787920
  • scopus:85089613340
ISSN
1478-6354
DOI
10.1186/s13075-020-02279-9
project
Monocytes and Neutrophils in Juvenile Idiopathic Arthritis
language
English
LU publication?
yes
id
4f410a1f-bf2f-46aa-ab3b-9230283198f4
date added to LUP
2020-08-14 09:20:54
date last changed
2024-01-17 09:22:06
@article{4f410a1f-bf2f-46aa-ab3b-9230283198f4,
  abstract     = {{Background<br>
Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).<br>
<br>
Methods<br>
Paired synovial fluid, blood samples (n = 13), and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization, and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence, and in situ hybridization.<br>
<br>
Results<br>
Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p &lt; 0.001), CD86 (p &lt; 0.001), and CD206 (p &lt; 0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p &lt; 0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies.<br>
<br>
Conclusion<br>
Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.}},
  author       = {{Schmidt, Tobias and Berthold, Elisabet and Arve-Butler, Sabine and Gullstrand, Birgitta and Mossberg, Anki and Kahn, Fredrik and Bengtsson, Anders and Månsson, Bengt and Kahn, Robin}},
  issn         = {{1478-6354}},
  language     = {{eng}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research & Therapy}},
  title        = {{Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment - a distinct inflammatory pattern for oligoarticular juvenile arthritis}},
  url          = {{http://dx.doi.org/10.1186/s13075-020-02279-9}},
  doi          = {{10.1186/s13075-020-02279-9}},
  volume       = {{22}},
  year         = {{2020}},
}