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Interleukin27 promotes inflammatory and neuroprotective responses in microglia

Kawanokuchi, J;Takeuchi, H;Sonobe, Y;

Objectives Interleukin-27 (IL-27) is released by antigen-presenting cells including macrophages, dendritic cells and microglia, and negatively regulates IL-17-producing T helper (Th17) cells, which play key pathogenic roles in multiple sclerosis. As the effects of IL-27 on cells in the central nervous system are unclear, we have examined the effects of IL-27 on microglia to uncover the roles of IL-27 in immune responses of the central nervous system. Methods The effects of IL-27 on microglial production of cytokines, neurotrophic factors and antigen-presentation related molecules were examined using reverse transcription polymerase chain reaction analyses and enzyme-linked immunosorbent assays. The effects of IL-27 on microglial antigen-presenting function were also assessed using coculture assays of microglia and myelin oligodendrocyte glycoprotein peptide 3555-specific T cells. Results We showed that IL-27 induces inflammatory and neuroprotective responses effects in microglia. IL-27 enhanced the production of nitric oxide and such pro-inflammatory cytokines as tumor necrosis factor- and IL-6 in lipopolysaccharide-activated microglia; these effects were not observed in unstimulated microglia, suggesting that IL-27 acts as an amplifier rather than an initiator of microglial neuroinflammation. IL-27 also enhanced microglial antigen presentation to promote Th1 polarization and suppress Th17 cell development by increasing IL-12 levels and reducing IL-23 levels. Furthermore, IL-27 increased microglial production of nerve growth factor, glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. Conclusions Our data suggest the therapeutic potential of IL-27 and microglia for multiple sclerosis through Th17 cell suppression and neurotrophic factor production.