Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells

IL-17 and IL-22 are typical cytokines produced by the Th17 T cell subset, but it is unclear if Th17 cytokines can be produced by other cell types. We demonstrate that IL-10-deficient and IL-10R-deficient macrophages stimulated with lipopolysaccharide produce high levels of IL-17 and IL-22. Addition of exogenous IL-10 to IL-10-deficient macrophages abolished IL-17 production. When IL-10-deficient and IL-10R-deficient splenocytes were cultured under Th17 polarizing conditions, the population of IL-17-producing cells was increased and the cultures produced significantly higher levels of IL-17 and IL-22. The addition of recombinant IL-10 to IL-10-deficient splenocytes significantly decreased the percentage of IL-17-producing CD4+ T cells. Finally, the mRNA for the Th17 transcription factor retinoic acid-related orphan receptor (ROR)γt was significantly elevated in IL-10-deficient spleen cells and macrophages. These data demonstrate that Th17 cytokines and RORct are also expressed in macrophages and that IL-10 negatively regulates the expression of Th17 cytokines and RORγt by both macrophages and T cells.