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MicroRNA-34a dependent regulation of AXL controls the activation of dendritic cells in inflammatory arthritis

Author

Listed:
  • Mariola Kurowska-Stolarska

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Stefano Alivernini

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Emma Garcia Melchor

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Aziza Elmesmari

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Barbara Tolusso

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Clare Tange

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Luca Petricca

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Derek S. Gilchrist

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Gabriele Di Sante

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Chantal Keijzer

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Lynn Stewart

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Clara Di Mario

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Vicky Morrison

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • James M. Brewer

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Duncan Porter

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Simon Milling

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Ronald D. Baxter

    (Institute of Infection, Immunity and Inflammation, University of Glasgow
    NHS Greater Glasgow and Clyde)

  • David McCarey

    (NHS Greater Glasgow and Clyde)

  • Elisa Gremese

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Greg Lemke

    (Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies)

  • Gianfranco Ferraccioli

    (Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart)

  • Charles McSharry

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

  • Iain B. McInnes

    (Institute of Infection, Immunity and Inflammation, University of Glasgow)

Abstract

Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance to pathogenesis by activating auto-reactive lymphocytes. Here we show that microRNA-34a provides homoeostatic control of CD1c+ DC activation via regulation of tyrosine kinase receptor AXL, an important inhibitory DC auto-regulator. This pathway is aberrant in CD1c+ DCs from patients with RA, with upregulation of miR-34a and lower levels of AXL compared to DC from healthy donors. Production of pro-inflammatory cytokines is reduced by ex vivo gene-silencing of miR-34a. miR-34a-deficient mice are resistant to collagen-induced arthritis and interaction of DCs and T cells from these mice are reduced and do not support the development of Th17 cells in vivo. Our findings therefore show that miR-34a is an epigenetic regulator of DC function that may contribute to RA.

Suggested Citation

  • Mariola Kurowska-Stolarska & Stefano Alivernini & Emma Garcia Melchor & Aziza Elmesmari & Barbara Tolusso & Clare Tange & Luca Petricca & Derek S. Gilchrist & Gabriele Di Sante & Chantal Keijzer & Lyn, 2017. "MicroRNA-34a dependent regulation of AXL controls the activation of dendritic cells in inflammatory arthritis," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15877
    DOI: 10.1038/ncomms15877
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    Cited by:

    1. Alessandra Nerviani & Marie-Astrid Boutet & Giulia Maria Ghirardi & Katriona Goldmann & Elisabetta Sciacca & Felice Rivellese & Elena Pontarini & Edoardo Prediletto & Federico Abatecola & Mattia Calis, 2024. "Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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