Abstracts (complete list) - Wissenschaft Online

Dorit Fabricius, Sue O’Dorisio, Sue Blackwell, Bernd Jahrsdörfer, Klaus-Michael Debatin
Inhibition of IFN-α Secretion and Modulation of
Immunophenotype and Stimulatory Capacity of Human
Plasmacytoid Dendritic Cell by Vasoactive Intestinal Peptide
Plasmacytoid dendritic cells (PDC) represent a central link between innate and adaptive
immunity. The special feature of PDC compared to other DC subsets is that they not
only are capable of antigen presentation but also unite the capacities of high IFN-α and
Granzyme B production. The increased frequency in various tumor tissues and in sites
of active autoimmune processes reflects an essential role of PDC both for tumor and
auto-immunity. While the role of granzyme B secretion by PDC is still unclear, excessive
IFN-α production seems to be a key factor in driving pathogenesis in certain
autoimmune diseases, mainly systemic lupus erythematodes. A better understanding of
PDC regulation is therefore crucial for more effective immunotherapeutic approaches to
cancer and autoimmunity. We show here that the neuropeptide vasoactive intestinal
peptide (VIP) significantly down-regulates IFN-α secretion by PDC and modulates PDC
immunophenotype. Furthermore, VIP inhibits the potential of PDC to induce proliferation
of allogeneic CD4+ T cells and VIP-treated PDC decrease the ratio of IFN-γ to IL-4
secreted by CD4+ T cells. We also demonstrate that PDC actively secrete the cytotoxic
molecule granzyme B, and that this process can be regulated by VIP and cytokines such
as interleukin 21 (IL-21). We conclude that modulation of PDC by VIP may be one
possible escape mechanism of malignancies that secrete this neuropeptide. In contrast,
VIP may turn out to be an exciting new candidate for immunotherapeutic intervention in
autoimmune diseases, since it suppresses the pathogenetically critical IFN-α secretion
and the T cell-stimulatory capacity of PDC.