Interleukin 10 Induces the Maturation of Putative Tolerogenic Monocyte-derived Dendritic Cells as Revealed by GeneArray Analysis

Abstract

IL-10 is a multifunctional cytokine with known inhibitory effect on DC maturation. In the present study, we show that the presence of IL-10 during the first 6 days of maturation of Mo-DC has severe effects on the phenotype with IL-10 treated Mo-DC retaining a high expression of factors involved in antigen uptake and having low expression of costimulatory factors and MHC II. The effect of IL-10 on DC maturation is further characterized by a comprehensive investigation of the expression profile of 12500 genes using GeneArrays and comparing the data for IL-10 treated and untreated Mo-DC at day 6 and 8 with monocytes and macrophages. The data is confirmed with semi-quantitative RT-PCR. We find that the transcriptional pattern of IL-10 treated Mo-DC at day 6 and day 8 is distinct from both untreated Mo-DC and macrophages. IL-10 induces the expression of genes coding for CCL18, ILT3, ILT4 and TGFβ while inhibiting the expression of IL-12 p40 mRNA, and genes coding for CCL17, CCL19 and CCL22 suggesting a likely effect of IL-10 on Mo-DC maturation to be the generation of tolerogenic Mo-DC.