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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

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...

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Autores principales: Schmidt, Tobias, Berthold, Elisabet, Arve-Butler, Sabine, Gullstrand, Birgitta, Mossberg, Anki, Kahn, Fredrik, Bengtsson, Anders A., Månsson, Bengt, Kahn, Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425414/
https://www.ncbi.nlm.nih.gov/pubmed/32787920
http://dx.doi.org/10.1186/s13075-020-02279-9
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author Schmidt, Tobias
Berthold, Elisabet
Arve-Butler, Sabine
Gullstrand, Birgitta
Mossberg, Anki
Kahn, Fredrik
Bengtsson, Anders A.
Månsson, Bengt
Kahn, Robin
author_facet Schmidt, Tobias
Berthold, Elisabet
Arve-Butler, Sabine
Gullstrand, Birgitta
Mossberg, Anki
Kahn, Fredrik
Bengtsson, Anders A.
Månsson, Bengt
Kahn, Robin
author_sort Schmidt, Tobias
collection PubMed
description 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.
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spelling pubmed-74254142020-08-16 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 Berthold, Elisabet Arve-Butler, Sabine Gullstrand, Birgitta Mossberg, Anki Kahn, Fredrik Bengtsson, Anders A. Månsson, Bengt Kahn, Robin Arthritis Res Ther Research Article 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. BioMed Central 2020-08-12 2020 /pmc/articles/PMC7425414/ /pubmed/32787920 http://dx.doi.org/10.1186/s13075-020-02279-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Schmidt, Tobias
Berthold, Elisabet
Arve-Butler, Sabine
Gullstrand, Birgitta
Mossberg, Anki
Kahn, Fredrik
Bengtsson, Anders A.
Månsson, Bengt
Kahn, Robin
Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title_full Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title_fullStr Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title_full_unstemmed Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title_short Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
title_sort children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425414/
https://www.ncbi.nlm.nih.gov/pubmed/32787920
http://dx.doi.org/10.1186/s13075-020-02279-9
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