Lipopolysaccharide-induced expression of TRAIL promotes dendritic cell differentiation.

Published

Journal Article

Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a death-inducing cytokine whose physiological function is not well understood. Here, we show that TRAIL has a role in programming human dendritic cell (DC) differentiation. TRAIL expression was strongly induced in DCs upon stimulation with lipopolysaccharide (LPS) or Polyinosine-polycytidylic acid (poly(I:C)) stimulation. Blockade of TRAIL with neutralizing antibody partially inhibited LPS-induced up-regulation of co-stimulatory molecules and the expression of inflammatory cytokines including interleukin-12 (IL-12) p70. In addition, neutralization of TRAIL in LPS-treated DCs inhibited the DC-driven differentiation of T cells into interferon-gamma (IFN-gamma) -producing effectors. The effects of TRAIL neutralization in poly(I:C)-treated DCs were similar, except that IL-12 production and the differentiation of effector T cells into IFN-gamma producers were not inhibited. Strikingly, TRAIL stimulation alone was sufficient to induce morphological changes resembling DC maturation, up-regulation of co-stimulatory molecules, and enhancement of DC-driven allogeneic T-cell proliferation. However, TRAIL alone did not induce inflammatory cytokine production. We further show that the effects of TRAIL on DC maturation were not the result of the induction of apoptosis, but may involve p38 activation. Hence, our data demonstrate that TRAIL co-operates with other cytokines to facilitate DC functional maturation in response to Toll-like receptor activation.

Full Text

Duke Authors

Cited Authors

  • Cho, YS; Challa, S; Clancy, L; Chan, FK-M

Published Date

  • August 2010

Published In

Volume / Issue

  • 130 / 4

Start / End Page

  • 504 - 515

PubMed ID

  • 20406302

Pubmed Central ID

  • 20406302

Electronic International Standard Serial Number (EISSN)

  • 1365-2567

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2567.2010.03266.x

Language

  • eng

Conference Location

  • England