Submitted December 12, 2007
Accepted April 8, 2008
CD300a/c regulate type I interferon and TNF-
secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands
Xinsheng Ju, Martin Zenke, Derek NJ Hart, and Georgina J Clark*
Dendritic Cell Program, Mater Medical Research Institute, Brisbane, Qld, Australia
Institute for Biomedical Engineering, Department of Cell Biology, Aachen University Hospital, Aachen, Germany
* Corresponding author; email: gclark{at}mmri.mater.org.au.
Activation of human plasmacytoid dendritic cells (pDC) with ligands for Toll-like receptors (TLRs) 7 and 9 induces the secretion of type I interferons and other inflammatory cytokines as well as pDC differentiation. Transcripts for two members of the CD300 gene family, CD300a and CD300c, were identified on pDC during gene expression studies to identify new immunoregulatory molecules on pDC. We therefore investigated the expression of CD300a and CD300c and their potential regulation of pDC function. CD300a/c RNA and surface expression were downregulated following stimulation of pDC with TLR7 and TLR9 ligands. Exogenous IFN-
downregulated CD300a/c expression, whilst neutralizing IFN- abolished TLR ligand induced CD300a/c downregulation. This implicates IFN- in regulating CD300a/c expression in pDC. Additionally, IFN- favored TNF- secretion by CpG induced pDC. CD300a/c triggering by crosslinking antibody reduced TNF- and increased IFN- secretion by pDC. Furthermore, CD300a/c triggering, in the presence of neutralizing IFN-, further reduced TNF- secretion. These data indicate that CD300a and CD300c play an important role in the cross-regulation of TNF- and IFN- secretion from pDC.
