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The DC-derived protein DC-STAMP influences differentiation of myeloid cells

Leukemia volume 22, pages 455–459 (2008)Cite this article

Fully differentiated myeloid cells are derived from a common myeloid precursor, which resides in the bone marrow. Depending on activities of cytokines and transcription factors, the differentiation of the common myeloid precursor gives rise to granulocyte/macrophage progenitors, megakaryocyte/erythroid progenitors and mast cell/basophil progenitors.1 The granulocyte/macrophage progenitors further branch into neutrophilic granulocytes or macrophages, dendritic cells and osteoclasts.2 The development of dendritic cells is stimulated in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF).

Interestingly, both GM-CSF and IL-4 are also potent inducers of the recently discovered protein DC-STAMP (dendritic cell specific transmembrane protein). DC-STAMP is a novel 470 amino-acid protein preferentially expressed in myeloid DC, macrophages and osteoclasts.3, 4, 5 DC-STAMP is a conserved multi-membrane spanning protein, with little or no homology to other known proteins.3, 4, 6 Although the function of DC-STAMP in DC is unknown, recent data indicate a role for DC-STAMP in macrophage and osteoclast fusion.5 DC-STAMP mRNA is expressed at very low levels in undifferentiated bone marrow cells and monocytes. Upon differentiation of these cells towards DC or macrophage using IL-4 and GM-CSF, DC-STAMP mRNA levels increase and parallel the increase in the expression of CD11c.3, 4, 6 In freshly isolated spleen cells, DC-STAMP mRNA expression is predominantly restricted to CD11cpos cells and is hardly detectable in CD11cneg cells, including granulocytes.6 Thus, the expression of DC-STAMP appears to be limited to cells belonging to the common myeloid precursor-derived branch that comprises macrophages, DC and osteoclasts and it is not expressed in neutrophilic granulocytes belonging to the other branch. This expression pattern plus the induction of DC-STAMP by IL-4, which controls the branching in granulocyte/macrophage progenitors development, suggest that DC-STAMP may play a role in the control of myeloid differentiation. We investigated this hypothesis by overexpressing DC-STAMP in murine bone marrow progenitor cells, which were subsequently cultured in various differentiation-inducing conditions.

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Acknowledgements

We thank Desiré van Steenhoven, Erik Bennink, Martijn den Brok, Maaike van Hout (Department of Tumor Immunology), Ruth Knops, Gertie Vierwinden, Peter Linssen and Aswin Menke (Central Hematology Laboratory) for technical assistance and valuable advice. This research is supported in part by grants from The Netherlands Organization for Scientific Research (912-02-034 and 901-10-092).

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Author notes

  1. R A J Janssen

    Present address: 4Current address: Galádeno, Archimedesweg 4, 2333 GN Leiden, The Netherlands,

  2. I A M Hendriks & V Moulin

    Present address: 5Current address: Intervet, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands,

  3. D Eleveld-Trancikova and R A J Janssen: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    D Eleveld-Trancikova, R A J Janssen, I A M Hendriks, M W G Looman, V Moulin, B J H Jansen, C G Figdor & G J Adema

  2. Central Hematology Laboratory, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. E-mail: g.adema@ncmls.ru.nl,

    J H Jansen

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Eleveld-Trancikova, D., Janssen, R., Hendriks, I. et al. The DC-derived protein DC-STAMP influences differentiation of myeloid cells. Leukemia 22, 455–459 (2008). https://doi.org/10.1038/sj.leu.2404910

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