Paradoxical effects of interleukin‐10 on the maturation of murine myeloid dendritic cells

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Abstract
Summary: The immunoregulatory cytokine, interleukin‐10 (IL‐10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL‐10 has paradoxical effects on the maturation of murine myeloid bone marrow‐derived DC. On the one hand, IL‐10 inhibits the maturation of murine myeloid DC. The addition of IL‐10 to granulocyte–macrophage colony‐stimulating factor (GM‐CSF)‐supported murine BM‐derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL‐10‐pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL‐10 on human DC, we found that the addition of IL‐10 from the initiation of the culture onwards induced an up‐regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM‐CSF only. Moreover, a subpopulation of IL‐10‐pretreated MHC class IIdim DC lacked the capacity to take up dextran‐fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL‐10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T‐cell stimulatory capacity, suggesting a role for IL‐10 in conferring tolerogenic properties on murine myeloid DC.

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