Frontiers in Immunology (Mar 2016)

TLR3 signaling promotes the induction of unique human BDCA3 dendritic cell populations

  • Nicholas eColletti,
  • Hong eLiu,
  • Adam eGower,
  • Yuriy eAlekseyev,
  • Christopher eArendt,
  • Michael eShaw

DOI
https://doi.org/10.3389/fimmu.2016.00088
Journal volume & issue
Vol. 7

Abstract

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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 (TLR) 3 and upon stimulation with Poly:IC secrete IFN-β, CXCL10, and IL-12p70. In this article, we show that activation of human BDCA-3 DCs with Poly:IC induces the expression of activation markers (CD40, CD80, and CD86) and immunoglobulin-like transcript (ILT) 3 and 4. This Poly:IC 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 BDCA3 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.

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