CD300a/c regulate type I interferon and TNF-α secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands

Abstract

AbstractActivation of human plasmacytoid dendritic cells (pDCs) 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 2 members of the CD300 gene family, CD300a and CD300c, were identified on pDCs during gene expression studies to identify new immunoregulatory molecules on pDCs. We therefore investigated the expression of CD300a and CD300c and their potential regulation of pDC function. CD300a/c RNA and surface expression were downregulated after stimulation of pDCs with TLR7 and TLR9 ligands. Exogenous interferon (IFN)-α down-regulated CD300a/c expression, whereas neutralizing IFN-α abolished TLR ligand–induced CD300a/c down-regulation. This implicates IFN-α in regulating CD300a/c expression in pDCs. In addition, IFN-α favored tumor necrosis factor (TNF)-α secretion by CpG-induced pDCs. CD300a/c triggering by cross-linking antibody reduced TNF-α and increased IFN-α secretion by pDCs. Furthermore, CD300a/c triggering, in the presence of neutralizing IFN-α, further reduced TNF-α secretion. These data indicate that CD300a and CD300c play an important role in the cross-regulation of TNF-α and IFN-α secretion from pDCs.