slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation

Blood. 2015 Dec 10;126(24):2601-10. doi: 10.1182/blood-2015-06-651331. Epub 2015 Oct 6.


Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+) intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c(+) dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / analysis*
  • Antigens, CD1 / analysis
  • Dendritic Cells / chemistry
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / analysis
  • Gene Expression Profiling
  • Genes, MHC Class II
  • Genome-Wide Association Study
  • Glycoproteins / analysis
  • HLA-D Antigens / analysis
  • Humans
  • Immunomagnetic Separation
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / immunology
  • Leukoencephalopathies / pathology
  • Lipopolysaccharide Receptors / analysis
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Monocytes / classification*
  • Monocytes / immunology
  • Point Mutation
  • Receptor, Macrophage Colony-Stimulating Factor / genetics*
  • Receptors, IgG / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoidosis / immunology
  • Sarcoidosis / pathology
  • Young Adult


  • 6-sulfo-LacNac
  • Amino Sugars
  • Antigens, CD1
  • CD1C protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Glycoproteins
  • HLA-D Antigens
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Receptor, Macrophage Colony-Stimulating Factor

Supplementary concepts

  • Hereditary Diffuse Leukoencephalopathy with Spheroids