title: TLR3 Signaling Promotes the Induction of Unique Human BDCA-3 Dendritic Cell Populations.
abstract: Conventional and plasmacytoid dendritic cells (cDCs and pDCs) are the two populations of DCs that can be readily identified in human blood. Conventional DCs have been subdivided into CD1c(+), or blood dendritic cells antigen (BDCA) 1 and CD141(+), or BDCA-3, DCs, each having both unique gene expression profiles and functions. BDCA-3 DCs express high levels of toll-like receptor 3 and upon stimulation with Poly I:C secrete IFN-β, CXCL10, and IL-12p70. In this article, we show that activation of human BDCA-3 DCs with Poly I:C induces the expression of activation markers (CD40, CD80, and CD86) and immunoglobulin-like transcript (ILT) 3 and 4. This Poly I:C stimulation results in four populations identifiable by flow cytometry based on their expression of ILT3 and ILT4. We focused our efforts on profiling the ILT4(-) and ILT4(+) DCs. These ILT-expressing BDCA-3 populations exhibit similar levels of activation as measured by CD40, CD80, and CD86; however, they exhibit differential cytokine secretion profiles, unique gene signatures, and vary in their ability to prime allogenic naïve T cells. Taken together, these data illustrate that within a pool of BDCA-3 DCs, there are cells poised to respond differently to a given input stimulus with unique output of immune functions.
authors.affiliation: Sanofi Pharmaceuticals, Cambridge, MA, USA; Department of Biological Science, Seton Hall University, South Orange, NJ, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Colletti
authors.affiliation: Sanofi Pharmaceuticals , Cambridge, MA , USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Clinical and Translational Science Institute, Boston University , Boston, MA , USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Gower
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University , Boston, MA , USA.
authors.forename: Yuriy O
authors.initials: YO
authors.lastname: Alekseyev
authors.affiliation: Sanofi Pharmaceuticals , Cambridge, MA , USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Arendt
authors.affiliation: Sanofi Pharmaceuticals , Cambridge, MA , USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shaw
keywords: BDCA-3; ILT3; ILT4; TLR3; dendritic cell