Dendritic cells (DCs) control the balance between effector T cells and regulatory T cells in vivo. Hence, the study of DCs might identify mechanisms of disease pathogenesis and guide new therapeutic approaches for disorders mediated by the immune system. We found that interleukin 27 (IL-27) signaling in mouse DCs limited the generation of effector cells of the TH1 and TH17 subsets of helper T cells and the development of experimental autoimmune encephalomyelitis (EAE). The effects of IL-27 were mediated at least in part through induction of the immunoregulatory molecule CD39 in DCs. IL-27-induced CD39 decreased the extracellular concentration of ATP and downregulated nucleotide-dependent activation of the NLRP3 inflammasome. Finally, therapeutic vaccination with IL-27-conditioned DCs suppressed established relapsing-remitting EAE. Thus, IL-27 signaling in DCs limited pathogenic T cell responses and the development of autoimmunity.
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We thank A. Sharpe (Harvard Medical School) for PD-L1 deficient mice; D.J. Pinsky (University of Michigan Health Systems) for the Entpd1 promoter reporter; and D. Frank (Dana-Farber Cancer Institute, Boston) for vectors encoding constitutively active STAT3 and STAT1. Supported by the US National Institutes of Health (AI075285 and AI093903 to F.J.Q.) and the National Multiple Sclerosis Society (RG4111A1 to F.J.Q.).
The authors declare no competing financial interests.
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Mascanfroni, I., Yeste, A., Vieira, S. et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 14, 1054–1063 (2013). https://doi.org/10.1038/ni.2695
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