Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

J Exp Med. 2012 Jan 16;209(1):109-21. doi: 10.1084/jem.20110399. Epub 2012 Jan 2.


Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology*
  • Antigens / metabolism
  • Asialoglycoprotein Receptor / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Interleukin-10 / biosynthesis*
  • Ligands
  • Macaca
  • Male
  • Scavenger Receptors, Class E / metabolism
  • Signal Transduction


  • Antigens
  • Asialoglycoprotein Receptor
  • Ligands
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • Interleukin-10
  • Extracellular Signal-Regulated MAP Kinases