IT9302,
a nanomeric peptide (AYMTMKIRN), homologous
to the C-terminal of the human IL-10 sequence,
was previously demonstrated by us, to mimic
several described effects of the cytokine,
including down-regulation of MHC class I
and TAP1 and TAP2 expression in human melanomas
and increasing of tumor sensitivity to NK
cells. In several other studies, IL-10 has
been demonstrated to inhibits monocyte-dendritic
cells (DC) differentiation, mediated by
GMCSF and IL-4, and maturation of DC, affecting
the expression of several DC surface markers
including CD36, CD83, MHC class I and Class
II. In the present report, we have investigated
the in vitro effect of the peptide IT9302
in the differentiation of monocytes derived
DC, and in the maturation of DC. Our results
showed that the peptide can prevent the
differentiation of monocytes to DC mediated
by IL-4 and GM-CSF, affecting the expression
of MHC class I, MHC class II, CD36 and CD14
markers. |
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Similarly,
TNF-alpha induced maturation of immature
DC after six days in vitro incubation can
be avoided by the presence of IT9302 peptide
or rhIL-10, affecting also MHC class I and
II expression and also CD83. These phenotypic
changes are in line with observed functional
changes on peptide treated DC, including
phagocytic capacity, DC mediated induction
of allogenic T cell proliferation and DC
induced IFN-? production by T cells. In
summary, DC produced in the presence of
IT9302 have phenotypic and functional properties
of associated to inhibitory DC cells. The
capability of produce in vitro inhibitory
DC cells using a synthetic peptide may be
a valuable tool in the immune therapy of
autoimmune diseases.
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