Contribution of microRNA 24–3p and Erk1/2 to interleukin-6-mediated plasma cell survival

Authors

  • Jessica Gabler,

    1. Department of Pediatrics, Philipps University Marburg, Marburg, Germany
    2. Research Centre for Experimental Orthopaedics, Orthopaedic University Hospital Heidelberg, Heidelberg, Germany
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  • Jürgen Wittmann,

    1. Division of Molecular Immunology, Nikolaus-Fiebiger Center, University Erlangen-Nürnberg, Erlangen, Germany
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  • Martina Porstner,

    1. Division of Molecular Immunology, Nikolaus-Fiebiger Center, University Erlangen-Nürnberg, Erlangen, Germany
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  • Harald Renz,

    1. Biomedical Research Center (BMFZ), Institute of Laboratory Medicine, Philipps University of Marburg, Marburg, Germany
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  • Hans-Martin Jäck,

    1. Division of Molecular Immunology, Nikolaus-Fiebiger Center, University Erlangen-Nürnberg, Erlangen, Germany
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  • Melanie Abram,

    1. Department of Pediatrics, Philipps University Marburg, Marburg, Germany
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    • These authors contributed equally to this work.

  • Michael Zemlin

    Corresponding author
    1. Department of Pediatrics, Philipps University Marburg, Marburg, Germany
    • Full correspondence: Dr. Michael Zemlin, Department of Pediatrics, Philipps University Marburg, Baldingerstr. 1, 35033 Marburg, Germany

      Fax: +49-6421-5868970

      e-mail: zemlin@staff.uni-marburg.de

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    • These authors contributed equally to this work.


Abstract

Plasma cells can survive for long periods and continuously secrete protective antibodies, but plasma cell production of autoantibodies or transformation to tumor cells is detrimental. Plasma cell survival depends on exogenous factors from the surrounding microenvironment, and largely unknown intracellular mediators that regulate cell homeostasis. Here we investigated the contribution of the microRNA 24–3p (miR-24–3p) to the survival of human plasma cells under the influence of IL-6 and SDF-1α (stromal cell derived factor 1), both of which are bone marrow survival niche mediators. Deep sequencing revealed a strong expression of miR-24–3p in primary B cells, plasma blasts, plasma cells, and in plasmacytoma cells. In vitro studies using primary cells and the plasmacytoma cell line RPMI-8226 revealed that (i) expression of miR-24–3p mediates plasma cell survival, (ii) miR-24–3p is upregulated by IL-6 and SDF-1α, (iii) IL-6 mediates cell survival under ER stress conditions via miR-24–3p expression, and (iv) IL-6-induced miR-24–3p expression depends on the activity of the MAP kinase Erk1/2. These results suggest a direct connection between an external survival signal and an intracellular microRNA in regulating plasma cell survival. miR-24–3p could therefore be a promising target for new therapeutic strategies for autoimmune and allergic diseases and for multiple myeloma.

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