biostudies-literature00530Breton GNCRR NIH HHSHoward Hughes Medical InstituteNIAID NIH HHSNINDS NIH HHSNIAMS NIH HHS401-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC4354370biostudies-literatureUnknown212(3)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.The Journal of experimental medicineCirculating precursors of human CD1c+ and CD141+ dendritic cells.PMC4354370R01 AI101251U19 AI111825AR063461-01A1AI101251NS084776AI13013UL1 RR024143U19AI111825K23 AR063461F31 NS084776R01 AI013013UL1RR024143Breton GSchreiber JJLiu KNussenzweig MCZhou YJPuhr SSchlesinger SLee JAnandasabapathy NCaskey MKeler T53falseCirculating precursors of human CD1c+ and CD141+ dendritic cells.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.2015-01-01T00:00:00Z2015 Mar2021-02-21T02:38:33Z2019-03-27T01:47:53ZS-EPMC43543702568728110.1084/jem.20141441