Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis

Abstract Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured...

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Autores principales:	Ditte Køster, Johanne Hovgaard Egedal, Søren Lomholt, Malene Hvid, Martin R. Jakobsen, Ulf Müller-Ladner, Hermann Eibel, Bent Deleuran, Tue Wenzel Kragstrup, Elena Neumann, Morten Aagaard Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/534b11d35cf043f5b6353f63fbcc17d0
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spelling	oai:doaj.org-article:534b11d35cf043f5b6353f63fbcc17d02021-11-14T12:17:44ZPhenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis10.1038/s41598-021-01692-72045-2322https://doaj.org/article/534b11d35cf043f5b6353f63fbcc17d02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01692-7https://doaj.org/toc/2045-2322Abstract Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.Ditte KøsterJohanne Hovgaard EgedalSøren LomholtMalene HvidMartin R. JakobsenUlf Müller-LadnerHermann EibelBent DeleuranTue Wenzel KragstrupElena NeumannMorten Aagaard NielsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ditte Køster Johanne Hovgaard Egedal Søren Lomholt Malene Hvid Martin R. Jakobsen Ulf Müller-Ladner Hermann Eibel Bent Deleuran Tue Wenzel Kragstrup Elena Neumann Morten Aagaard Nielsen Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
description	Abstract Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.
format	article
author	Ditte Køster Johanne Hovgaard Egedal Søren Lomholt Malene Hvid Martin R. Jakobsen Ulf Müller-Ladner Hermann Eibel Bent Deleuran Tue Wenzel Kragstrup Elena Neumann Morten Aagaard Nielsen
author_facet	Ditte Køster Johanne Hovgaard Egedal Søren Lomholt Malene Hvid Martin R. Jakobsen Ulf Müller-Ladner Hermann Eibel Bent Deleuran Tue Wenzel Kragstrup Elena Neumann Morten Aagaard Nielsen
author_sort	Ditte Køster
title	Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
title_short	Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
title_full	Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
title_fullStr	Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
title_full_unstemmed	Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
title_sort	phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/534b11d35cf043f5b6353f63fbcc17d0
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Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis

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