Differential production of inflammatory chemokines by murine dendritic cell subsets

Immunobiology. 2004;209(1-2):163-72. doi: 10.1016/j.imbio.2004.03.002.

Abstract

Dendritic cells (DC) are efficient antigen presenting cells with the ability to activate naïve T cells. Murine DC represent a heterogeneous population that can be subdivided into distinct subsets, including the conventional DC (cDC) which are either CD4(-)CD8(-) (DN), CD4(+)CD8(-) (CD4+) or CD4(-)CD8(+) (CD8+) subsets and the plasmacytoid DC (pDC), which have different immune regulatory functions. In this study, we investigated the differential expression of genes encoding the inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes, and the secretion of these chemokines, among splenic DC subsets. These chemokine genes were expressed at higher levels by the splenic CD4+ and DN cDC subsets compared with the CD8+ cDC, in both the resting and activated states in vivo. Both the pDC and cDC subsets displayed increases in chemokine secretion in response to a range of toll-like receptor (TLR) stimuli in vitro. Whilst the pDC were the highest producers of Mip-1alpha and Mip-1beta in response to some TLR stimuli, the DN and CD4+ cDC subsets were the superior producers of Rantes. Overall, of the cDC, the CD4+ cDC produced all chemokines most efficiently, both at a basal level, and in response to most TLR stimuli. Thus, we report a new functional difference between the murine splenic cDC subsets, with the CD4+ cDC demonstrating the most efficient production of the inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes.

MeSH terms

  • Animals
  • Cell Differentiation
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokines / biosynthesis*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Macrophage Inflammatory Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / metabolism

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Macrophage Inflammatory Proteins