CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease

Nat Immunol. 2008 Nov;9(11):1253-60. doi: 10.1038/ni.1658. Epub 2008 Oct 5.

Abstract

Dendritic cells (DCs) are 'professional' antigen-presenting cells that are key in the regulation of immune responses. Here we characterize a unique subset of tolerogenic DCs that expressed the chemokine receptor CCR9 and migrated to the CCR9 ligand CCL25, a chemokine linked to the homing of T cells and DCs to the gut. CCR9(+) DCs were of the plasmacytoid DC (pDC) lineage, had an immature phenotype and rapidly downregulated CCR9 in response to maturation-inducing pDC-restricted Toll-like receptor ligands. CCR9(+) pDCs were potent inducers of regulatory T cell function and suppressed antigen-specific immune responses both in vitro and in vivo, including inhibiting acute graft-versus-host disease induced by allogeneic CD4(+) donor T cells in irradiated recipients. Our results identify a highly immunosuppressive population of pDCs present in lymphoid tissues.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Chemokines, CC / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Down-Regulation
  • Graft vs Host Disease / immunology*
  • Intestines / immunology
  • Leukocyte Common Antigens / metabolism
  • Ligands
  • Mice
  • Mice, Congenic
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, CCR10 / immunology*
  • Receptors, CCR10 / metabolism
  • Self Tolerance*
  • T-Lymphocytes, Regulatory / immunology
  • Toll-Like Receptors / metabolism
  • Transplantation Tolerance*

Substances

  • Biomarkers
  • Ccl25 protein, mouse
  • Chemokines, CC
  • Ligands
  • Receptors, CCR10
  • Toll-Like Receptors
  • chemokine receptor D6
  • Leukocyte Common Antigens
  • Ptprc protein, mouse