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The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues

Nature Immunology volume 9, pages 676–683 (2008)Cite this article

Abstract

Dendritic cell (DC) development begins in the bone marrow but is not completed until after immature progenitors reach their sites of residence in lymphoid organs. The hematopoietic growth factors regulating these processes are poorly understood. Here we examined the effects of signaling by the receptor tyrosine kinase Flt3 on macrophage DC progenitors in the bone marrow and on peripheral DCs. We found that the macrophage DC progenitor compartment was responsive to superphysiological amounts of Flt3 ligand but was not dependent on Flt3 for its homeostatic maintenance in vivo. In contrast, Flt3 was essential to the regulation of homeostatic DC development in the spleen, where it was needed to maintain normal numbers of DCs by controlling their division in the periphery.

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Figure 1: Identification of cDC progenitors.
Figure 2: Effects of stimulation with Flt3L.
Figure 3: Myeloid compartments of Flt3−/− mice.
Figure 4: DC development in Flt3−/− bone marrow chimeras.
Figure 5: Flt3 in peripheral expansion.

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Acknowledgements

We thank Amgen for recombinant human Flt3L; I. Lemischka (Mount Sinai School of Medicine) for Flt3−/− mice; L. Robb (Walter and Eliza Hall Institute of Medical Research) and G. Begley (Amgen) for mice deficient in GM-CSF receptor-α; C.G. Park (Rockefeller University) for monoclonal antibodies to CD169 and SIGNR1; R. Steinman and A. Kamphorst for critical reading of the manuscript; and M. Suarez–Farinas for help with statistical analysis.

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Authors and Affiliations

  1. Laboratory of Molecular Immunology, The Rockefeller University, New York, 10065, New York, USA

    Claudia Waskow, Kang Liu, Guillaume Darrasse-Jèze, Pierre Guermonprez, Tamara Shengelia, Kaihui Yao & Michel Nussenzweig

  2. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, 10029, New York

    Florent Ginhoux & Miriam Merad

  3. Howard Hughes Medical Institute, The Rockefeller University, New York, 10065, New York, USA

    Michel Nussenzweig

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  1. Claudia Waskow
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Correspondence to Claudia Waskow.

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Waskow, C., Liu, K., Darrasse-Jèze, G. et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol 9, 676–683 (2008). https://doi.org/10.1038/ni.1615

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