IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39


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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Figure 1: IL-27RA expression in DCs.
Figure 2: IL-27 modulates the antigen-presenting function of cDCs.
Figure 3: IL-27RA signaling in cDCs controls T cell differentiation and EAE development.
Figure 4: CD39 is required for the inhibitory effects of IL-27 on DCs.
Figure 5: IL-27-induced CD39 controls extracellular ATP and activation of the NLRP3 inflammasome.
Figure 6: CD39 in DCs controls T cell differentiation and EAE development.
Figure 7: Vaccination with IL-27-conditioned DCs suppresses EAE.

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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.).

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I.D.M., A.Y., S.M.V., E.J.B., Y.W. and L.M. did in vitro and in vivo experiments; B.P., I.S., R.B.-H. and S.E. did bioinformatics analysis; V.K.K. and S.C.R. provided Il27ra−/− and Entpd1−/− mice; I.D.M. and F.J.Q. wrote the manuscript; and F.J.Q. supervised the study and edited the manuscript.

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Correspondence to Francisco J Quintana.

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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).

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