Nussenzweig MC:Circulating precursors of human CD1c+ and CD141+ dendritic cells

Source: Hits: 516 Pubdate: 2015-04-10

Abstract: Twosubsets of conventional dendritic cells (cDCs) withdistinct cell surfacemarkers and functions exist in mouse and human. The twosubsets of cDCs arespecialized antigen-presenting cells that initiate T cellimmunity andtolerance. In the mouse, a migratory cDC precursor (pre-CDC)originates fromdefined progenitors in the bone marrow (BM). Small numbers ofshort-livedpre-CDCs travel through the blood and replace cDCs in the peripheralorgans,maintaining homeostasis of the highly dynamic cDC pool. However, theidentityand distribution of the immediate precursor to human cDCs has not beendefined.Using a tissue culture system that supports the development of humanDCs, weidentify a migratory precursor (hpre-CDC) that exists in human cordblood, BM,blood, and peripheral lymphoid organs. hpre-CDCs differ frompremonocytes thatare restricted to the BM. In contrast to earlier progenitorswith greaterdevelopmental potential, the hpre-CDC is restricted to producingCD1c(+) andCD141(+) Clec9a(+) cDCs. Studies in human volunteers demonstratethat hpre-CDCsare a dynamic population that increases in response to levels ofcirculatingFlt3L.