Origin of the Lamina Propria Dendritic Cell Network

Immunity. 2009 Sep 18;31(3):513-25. doi: 10.1016/j.immuni.2009.08.010. Epub 2009 Sep 10.

Abstract

CX(3)CR1(+) and CD103(+) dendritic cells (DCs) in intestinal lamina propria play a key role in mucosal immunity. However, the origin and the developmental pathways that regulate their differentiation in the lamina propria remain unclear. We showed that monocytes gave rise exclusively to CD103(-)CX(3)CR1(+) lamina propria DCs under the control of macrophage-colony-stimulating factor receptor (M-CSFR) and Fms-like thyrosine kinase 3 (Flt3) ligands. In contrast, common DC progenitors (CDP) and pre-DCs, which give rise to lymphoid organ DCs but not to monocytes, differentiated exclusively into CD103(+)CX(3)CR1(-) lamina propria DCs under the control of Flt3 and granulocyte-macrophage-colony-stimulating factor receptor (GM-CSFR) ligands. CD103(+)CX(3)CR1(-) DCs but not CD103(-)CX(3)CR1(+) DCs in the lamina propria constitutively expressed CCR7 and were the first DCs to transport pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes. Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CX3C Chemokine Receptor 1
  • Cell Differentiation
  • Cell Lineage*
  • Cell Movement
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Integrin alpha Chains / immunology
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / immunology*
  • Lymph Nodes / immunology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptor, Macrophage Colony-Stimulating Factor / immunology
  • Receptors, Chemokine / immunology
  • Salmonella / immunology
  • Salmonella / pathogenicity
  • fms-Like Tyrosine Kinase 3 / deficiency
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / immunology

Substances

  • Antigens, CD
  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Integrin alpha Chains
  • Receptors, Chemokine
  • alpha E integrins
  • Flt3 protein, mouse
  • Receptor, Macrophage Colony-Stimulating Factor
  • fms-Like Tyrosine Kinase 3