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Blood, 23 July 2009, Vol. 114, No. 4, pp. 835-843. Prepublished online as a Blood First Edition Paper on May 22, 2009; DOI 10.1182/blood-2009-02-206318. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-02-206318v1 114/4/835    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Kingston, D. Articles by Manz, M. G. PubMed PubMed Citation Articles by Kingston, D. Articles by Manz, M. G. Related Collections Hematopoiesis and Stem Cells Immunobiology Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis Dior Kingston1, Michael A. Schmid1, Nobuyuki Onai13, Aya Obata-Onai13, Dirk Baumjohann1, and Markus G. Manz1 1 Institute for Research in Biomedicine, Bellinzona, Switzerland; 2 Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan; and 3 Japan Science and Technology Agency, Core Research of Evolutional Science & Technology (CREST), Tokyo, Japan Dendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are not defined. Here, we show that, although Gm-csfr and Flt3 are both expressed in DC progenitors, Gm-csfr is expressed predominantly in monocytes, classical DCs (cDCs), and skin DCs, whereas Flt3 is expressed in both cDCs and plasmacytoid DCs (pDCs). In accordance with the respective cytokine receptor expression, DC progenitor and pDC numbers are primarily affected by Flt3-ligand deficiency, whereas both splenic and lymph node cDCs and dermal DCs are reduced in the absence of either GM-CSF or Flt3-ligand. Combined lack of GM-CSF and Flt3-ligand in newly generated double-deficient mice leads to further significant reductions of DC progenitors and dermal DCs. In line with the decrease of respective DC subsets, T-cell and antigen-specific IgG responses decline progressively, from wild-type to GM-CSF– to Flt3-ligand– to double-deficient mice, upon subcutaneous antigen delivery. These data thus show the concerted action of GM-CSF and Flt3-ligand on DC homeostasis in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Hochweller, T. Miloud, J. Striegler, S. Naik, G. J. Hammerling, and N. Garbi Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop Blood, November 12, 2009; 114(20): 4411 - 4421. [Abstract] [Full Text] [PDF]

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