Human Dendritic Cells (DCs) Are Derived From Distinct Circulating Precursors That Are Precommitted to Become CD1c+ or CD141+ DCs

J Exp Med. 2016 Dec 12;213(13):2861-2870. doi: 10.1084/jem.20161135. Epub 2016 Nov 18.

Abstract

In humans, conventional dendritic cells (cDCs) exist as two unique populations characterized by expression of CD1c and CD141. cDCs arise from increasingly restricted but well-defined bone marrow progenitors that include the common DC progenitor that differentiates into the pre-cDC, which is the direct precursor of cDCs. In this study, we show that pre-cDCs in humans are heterogeneous, consisting of two distinct populations of precursors that are precommitted to become either CD1c+ or CD141+ cDCs. The two groups of lineage-primed precursors can be distinguished based on differential expression of CD172a. Both subpopulations of pre-cDCs arise in the adult bone marrow and can be found in cord blood and adult peripheral blood. Gene expression analysis revealed that CD172a+ and CD172a- pre-cDCs represent developmentally discrete populations that differentially express lineage-restricted transcription factors. A clinical trial of Flt3L injection revealed that this cytokine increases the number of both CD172a- and CD172a+ pre-cDCs in human peripheral blood.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, CD1 / metabolism*
  • Antigens, Differentiation / biosynthesis
  • Antigens, Surface / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation / physiology*
  • Glycoproteins / metabolism*
  • Humans
  • Receptors, Immunologic / biosynthesis
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antigens, CD1
  • Antigens, Differentiation
  • Antigens, Surface
  • CD1C protein, human
  • Glycoproteins
  • Receptors, Immunologic
  • SIRPA protein, human
  • blood dendritic cell antigen 3, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3