Therapeutical modulation of plasmacytoid dendritic cells in experimental arthritis - Archive ouverte HAL Access content directly
Journal Articles Arthritis & rheumatology Year : 2017

Therapeutical modulation of plasmacytoid dendritic cells in experimental arthritis

Ramzi Nehmar
  • Function : Author
  • PersonId : 1082076
Ghada Alsaleh-Alfarhan
  • Function : Author
  • PersonId : 948653
Benjamin Voisin
  • Function : Author
  • PersonId : 1082077
Vincent Flacher
Alexandre Mariotte
  • Function : Author
  • PersonId : 1082078
Victoria Saferding
  • Function : Author
Antonia Puchner
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Birgit Niederreiter
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Gernot Schabbauer
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M Holcmann
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Jean Sibilia
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  • PersonId : 1042337
Seiamak Bahram
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  • PersonId : 948652
S Bluml
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Philippe Georgel
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  • PersonId : 1055696

Abstract

OBJECTIVES: The role of plasmacytoid dendritic cells (pDCs) and type I Interferons in rheumatoid arthritis (RA) remains controversial. To explore their contribution to RA pathogenesis, we induced experimental arthritis in various animal models of pDC depletion. We also monitored the effect of localized pDC recruitment and activation on joint inflammation and bone damage. METHODS: Experimental arthritis in mice was obtained by K/BxN serum transfer, heterologous collagen immunization (CIA) or in hTNF-transgenics. Symptoms were followed by visual scoring, quantification of paw swelling, cytokine dosage by ELISA and histological analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptomic analysis (RT-qPCR) and flow cytometry of the periarticular tissue. RESULTS: pDC-deficient mice showed exacerbation of inflammatory and arthritic symptoms after arthritogenic serum transfer. In contrast, enhancing pDC recruitment and activation to arthritic joints by topical application of the TLR7 agonist Imiquimod significantly eased arthritis in various models. Imiquimod induces an interferon signature and leads to reduced infiltration of inflammatory cells. CONCLUSIONS: Therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR7 sensing by pDCs and type I interferon signaling. We suggest that local recruitment and activation of pDCs represent an attractive therapeutic opportunity for RA patients. This article is protected by copyright. All rights reserved.

Dates and versions

hal-03015609 , version 1 (19-11-2020)

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Ramzi Nehmar, Ghada Alsaleh-Alfarhan, Benjamin Voisin, Vincent Flacher, Alexandre Mariotte, et al.. Therapeutical modulation of plasmacytoid dendritic cells in experimental arthritis. Arthritis & rheumatology, 2017, pp.2124-2135. ⟨10.1002/art.40225⟩. ⟨hal-03015609⟩
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