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in Inducing Human Dendritic Cell Maturation
Centre d’Immunologie Pierre Fabre, Saint-Julien en Genevois, France
We investigated the effects of different neuropeptides on human
dendritic cells (DC) maturation. Immature DC, derived from monocytes
cultured for 6 days with IL-4 plus GM-CSF, have been exposed to
somatostatin, substance P, or vasoactive intestinal peptide (VIP).
Among these neuropeptides, only VIP induces the production of bioactive
IL-12 and the neoexpression of CD83 on a fraction of the DC population,
with an effect significant at 100 and 10 nM, respectively. These
effects of VIP are dose-dependent, unaffected by polymixin B, and
partly prevented by a VIP receptor antagonist. Although the effects of
VIP alone remain modest, it synergizes with TNF-
to induce DC
maturation. In the presence of a suboptimal concentration of TNF-,
which has no detectable effect on DC by itself, VIP induces the
production of high levels of bioactive IL-12, the neoexpression of CD83
on almost all the DC population (with an effect significant at 10 and
0.1 nM, respectively), and the up-regulation of various adhesion and
costimulatory molecule expression. Moreover, DC exposed to VIP plus a
suboptimal concentration of TNF- are as potent as mature DC obtained
by treatment with an optimal concentration of TNF- in stimulating
allogenic T cell proliferation. Our data suggest that, in inflammatory
sites, VIP may cooperate with proinflammatory mediators, such as
TNF-, to induce DC maturation.
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