A synthetic peptide homologous to functional domain of human IL-10 inhibits in vitro maturation and differentiation of human monocytes to dendritic cells.
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.
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.