Regulatory activity of autocrine IL-10 on dendritic cell functions

IL-10 is a critical cytokine that blocks the maturation of dendritic cells (DCs), but the relevance of autocrine IL-10 on DC functions has not been in vestigated. In this study, we found that immature monocyte-derived DCs rele ased low but sizeable amounts of IL-10. After stimulation with bacteria, LP S, lipoteichoic acid, or soluble CD40 ligand, DCs secreted high levels of I L-10. Addition of an anti-IL-10-neutralizing Ab to immature DCs as well as to soluble CD40 ligand- or LPS-maturing DCs led to enhanced expression of s urface CD83, CD80, CD86, and MHC molecules and markedly augmented release o f TNF-alpha and IL-12, but diminished IL-10 mRNA expression. Moreover, DCs treated with anti-IL-10 Ab showed an increased capacity to activate allogen eic T cells and primed naive T cells to a more prominent Th1 polarization. DC maturation and IL-10 neutralization were associated with enhanced accumu lation of the IL-10 receptor binding chain (IL-10R1) mRNA and intracellular IL-10R1 protein. In contrast, surface IL-10R1 and IL-10 binding activity d iminished in mature DCs. These results indicate that autocrine IL-10 preven ts spontaneous maturation of DCs in vitro, limits LPS- and CD40-mediated ma turation, and increases IL-10 production by DCs. Moreover, IL-10R expressio n appears to be regulated by both transcriptional and posttranscriptional m echanisms. Endogenous IL-10 and IL-10R can be relevant targets for the mani pulation of DC functions.