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Published Online March 12, 2009
Science DOI: 10.1126/science.1170540

Reports

Submitted on January 6, 2009
Accepted on March 4, 2009

In Vivo Analysis of Dendritic Cell Development and Homeostasis

Kang Liu 1*, Gabriel D. Victora 1{dagger}, Tanja A. Schwickert 1{dagger}, Pierre Guermonprez 1, Matthew M. Meredith 1, Kaihui Yao 1, Fei-Fan Chu 1, Gwendalyn J. Randolph 2, Alexander Y. Rudensky 3, Michel Nussenzweig 4*

1 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
2 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
3 Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
4 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.

* To whom correspondence should be addressed.
Kang Liu , E-mail: liuk{at}rockefeller.edu
Michel Nussenzweig , E-mail: nussen{at}rockefeller.edu

{dagger}These authors contributed equally to this work.

Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC and monocyte lineage commitment occurs and the nature of the DC precursor that migrates from the bone marrow to peripheral lymphoid organs is unknown. We show that DC development progresses from the macrophage and DC precursor (MDP), to common DC precursors (CDPs) that give rise to pDCs and classical spleen DCs (cDCs), but not monocytes, and finally to committed precursors of cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through and migrate along HEVs and later disperse and integrate into the DC network. Further cDC development involves cell division, controlled in part by regulatory T cells (Treg) and fms-related tyrosine kinase-3 (Flt3).


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