Deciphering the fate of slan + -monocytes in human tonsils by gene expression profiling

FASEB J. 2020 Jul;34(7):9269-9284. doi: 10.1096/fj.202000181R. Epub 2020 May 15.

Abstract

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.

Keywords: CD1c+DC/cDC2; blood; classical/non-classical monocytes; gene expression; slan+-monocytes; tonsil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / metabolism*
  • Case-Control Studies
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Gene Expression Profiling
  • Humans
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Palatine Tonsil / cytology
  • Palatine Tonsil / metabolism*
  • Tonsillitis / genetics*
  • Tonsillitis / metabolism
  • Tonsillitis / pathology

Substances

  • 6-sulfo-LacNac
  • Amino Sugars