Circulating precursors of human CD1c+ and CD141+ dendritic cells

J Exp Med. 2015 Mar 9;212(3):401-13. doi: 10.1084/jem.20141441. Epub 2015 Feb 16.

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.

Publication types

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

MeSH terms

  • Antigens, CD1 / metabolism*
  • Antigens, Surface / metabolism*
  • Cell Proliferation
  • Dendritic Cells / metabolism*
  • Fetal Blood / cytology
  • Glycoproteins / metabolism*
  • Humans
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Lymphoid Tissue / cytology
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Thrombomodulin
  • Tissue Culture Techniques

Substances

  • Antigens, CD1
  • Antigens, Surface
  • CD1C protein, human
  • Glycoproteins
  • Membrane Proteins
  • THBD protein, human
  • Thrombomodulin
  • flt3 ligand protein