Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions

TLDR

IL‑10 inhibits dendritic‑cell maturation, yet the role of autocrine IL‑10 and its receptor regulation in this process has not been explored, despite IL‑10 and IL‑10R being potential targets for modulating DC function. Autocrine IL‑10 produced by immature monocyte‑derived dendritic cells prevents spontaneous maturation, limits LPS‑ or CD40‑mediated maturation, and promotes IL‑10 production, while neutralizing IL‑10 enhances surface maturation markers, cytokine release, T‑cell activation, and Th1 polarization, and is associated with increased IL‑10R1 expression.

Abstract

Abstract 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 investigated. In this study, we found that immature monocyte-derived DCs released low but sizeable amounts of IL-10. After stimulation with bacteria, LPS, lipoteichoic acid, or soluble CD40 ligand, DCs secreted high levels of IL-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 surface CD83, CD80, CD86, and MHC molecules and markedly augmented release of TNF-α and IL-12, but diminished IL-10 mRNA expression. Moreover, DCs treated with anti-IL-10 Ab showed an increased capacity to activate allogeneic T cells and primed naive T cells to a more prominent Th1 polarization. DC maturation and IL-10 neutralization were associated with enhanced accumulation 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 diminished in mature DCs. These results indicate that autocrine IL-10 prevents spontaneous maturation of DCs in vitro, limits LPS- and CD40-mediated maturation, and increases IL-10 production by DCs. Moreover, IL-10R expression appears to be regulated by both transcriptional and posttranscriptional mechanisms. Endogenous IL-10 and IL-10R can be relevant targets for the manipulation of DC functions.