The inflammatory cytokine, GM-CSF, alters the developmental outcome of murine dendritic cells

Authors

  • Yifan Zhan,

    Corresponding author
    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
    • Full Correspondence: Dr. Yuekang Xu, Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria 3010, Australia.

      Fax: +61-3 9348 1421

      e-mail: yuekangx@unimelb.edu.au

      Additional correspondence: Dr. Yifan Zhan, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.

      Fax: +61-3 9347 0852

      e-mail: zhan@wehi.edu.au

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  • Javier Vega-Ramos,

    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
    3. Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia
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  • Emma M. Carrington,

    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
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  • Jose A. Villadangos,

    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
    3. Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia
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  • Andrew M. Lew,

    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
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  • Yuekang Xu

    Corresponding author
    1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
    3. Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia
    4. Anhui Medical University, Hefei, China
    • Full Correspondence: Dr. Yuekang Xu, Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria 3010, Australia.

      Fax: +61-3 9348 1421

      e-mail: yuekangx@unimelb.edu.au

      Additional correspondence: Dr. Yifan Zhan, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.

      Fax: +61-3 9347 0852

      e-mail: zhan@wehi.edu.au

    Search for more papers by this author

Abstract

Fms-like tyrosine kinase 3 ligand (Flt3L) is a major cytokine that drives development of dendritic cells (DCs) under steady state, whereas GM-CSF becomes a prominent influence on differentiation during inflammation. The influence GM-CSF exerts on Flt3L-induced DC development has not been thoroughly examined. Here, we report that GM-CSF alters Flt3L-induced DC development. When BM cells were cultured with both Flt3L and GM-CSF, few CD8+ equivalent DCs or plasmacytoid DCs developed compared to cultures supplemented with Flt3L alone. The disappearance of these two cell subsets in GM-CSF + Flt3L culture was not a result of simple inhibition of their development, but a diversion of the original differentiation trajectory to form a new cell population. As a consequence, both DC progeny and their functions were altered. The effect of GM-CSF on DC subset development was confirmed in vivo. First, the CD8+ DC numbers were increased under GM-CSF deficiency (when either GM-CSF or its receptor was ablated). Second, this population was decreased under GM-CSF hyperexpression (by transgenesis or by Listeria infection). Our finding that GM-CSF dominantly changes the regulation of DC development in vitro and in vivo has important implications for inflammatory diseases or GM-CSF therapy.

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