Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes

Immunity. 2006 Jun;24(6):767-77. doi: 10.1016/j.immuni.2006.03.020.

Abstract

Early and high-level production of IL-12 is crucial for effective immune responses against pathogens. Up until now, the cells providing this initial IL-12 have remained elusive. Here we show that a subset of human blood dendritic cells (DC) is the principal and primary source of IL-12p70 when blood leukocytes are stimulated with the TLR4-ligand LPS or with CD40-ligand. These so-called slanDC are characterized by the 6-sulfo LacNAc modification of PSGL-1, which is identified by the mAb M-DC8. The IL-12 response of slanDC requires a few hours of in vitro maturation, which is completely blocked in the presence of erythrocytes. This inhibition of maturation depends on the expression of CD47 on erythrocytes and of its ligand SIRPalpha on DC. While strictly controlled in the blood by erythrocytes, the high IL-12- and TNF-alpha-producing capacity of slanDC in tissues may be critical in fighting off pathogens; if uncontrolled, it may lead to adverse inflammatory reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation / metabolism
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • CD40 Ligand / pharmacology
  • CD47 Antigen / analysis
  • CD47 Antigen / metabolism
  • Coculture Techniques
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Erythrocytes / immunology*
  • Humans
  • Interleukin-12 / metabolism*
  • Ligands
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / immunology
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Receptors, Immunologic / analysis
  • Receptors, Immunologic / metabolism
  • Th1 Cells / immunology
  • Toll-Like Receptor 4 / agonists

Substances

  • 6-sulfo-LacNac
  • Amino Sugars
  • Antigens, Differentiation
  • CD47 Antigen
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Receptors, Immunologic
  • SIRPA protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • CD40 Ligand
  • Interleukin-12