title: Circulating precursors of human CD1c+ and CD141+ dendritic cells.
abstract: Two subsets of conventional dendritic cells (cDCs) with distinct cell surface markers and functions exist in mouse and human. The two subsets of cDCs are specialized antigen-presenting cells that initiate T cell immunity and tolerance. In the mouse, a migratory cDC precursor (pre-CDC) originates from defined progenitors in the bone marrow (BM). Small numbers of short-lived pre-CDCs travel through the blood and replace cDCs in the peripheral organs, maintaining homeostasis of the highly dynamic cDC pool. However, the identity and distribution of the immediate precursor to human cDCs has not been defined. Using a tissue culture system that supports the development of human DCs, we identify a migratory precursor (hpre-CDC) that exists in human cord blood, BM, blood, and peripheral lymphoid organs. hpre-CDCs differ from premonocytes that are restricted to the BM. In contrast to earlier progenitors with greater developmental potential, the hpre-CDC is restricted to producing CD1c(+) and CD141(+) Clec9a(+) cDCs. Studies in human volunteers demonstrate that hpre-CDCs are a dynamic population that increases in response to levels of circulating Flt3L.
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors: Gaëlle
authors: G
authors: Breton
authors: Columbia University Medical Center, Department of Microbiology and Immunology, New York, NY 10032.
authors: Jaeyop
authors: J
authors: Lee
authors: Columbia University Medical Center, Department of Microbiology and Immunology, New York, NY 10032.
authors: Yu Jerry
authors: YJ
authors: Zhou
authors: Hospital for Special Surgery, New York, NY 10021.
authors: Joseph J
authors: JJ
authors: Schreiber
authors: Celldex Therapeutics, Hampton, NJ 08827.
authors: Tibor
authors: T
authors: Keler
authors: Columbia University Medical Center, Department of Microbiology and Immunology, New York, NY 10032.
authors: Sarah
authors: S
authors: Puhr
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 Department of Dermatology Brigham and Women's Hospital, Boston, MA 02115.
authors: Niroshana
authors: N
authors: Anandasabapathy
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors: Sarah
authors: S
authors: Schlesinger
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors: Marina
authors: M
authors: Caskey
authors: Columbia University Medical Center, Department of Microbiology and Immunology, New York, NY 10032 kl2529@columbia.edu nussen@rockefeller.edu.
authors: Kang
authors: K
authors: Liu
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 kl2529@columbia.edu nussen@rockefeller.edu.
authors: Michel C
authors: MC
authors: Nussenzweig
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D018180:Thrombomodulin; D046509:Tissue Culture Techniques
chemical_list: D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; C546931:THBD protein, human; D018180:Thrombomodulin; C084881:flt3 ligand protein