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

Nature Immunology volume 14, pages 10541063 (2013) | Download Citation

Abstract

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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Acknowledgements

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.).

Author information

Author notes

    • Ivan D Mascanfroni
    •  & Ada Yeste

    These authors contributed equally to this work.

Affiliations

  1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Ivan D Mascanfroni
    • , Ada Yeste
    • , Silvio M Vieira
    • , Evan J Burns
    • , Bonny Patel
    • , Lior Mayo
    • , Vijay K Kuchroo
    •  & Francisco J Quintana
  2. The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.

    • Ido Sloma
    • , Rotem Ben-Hamo
    •  & Sol Efroni
  3. Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

    • Yan Wu
    •  & Simon C Robson

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Francisco J Quintana.

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DOI

https://doi.org/10.1038/ni.2695

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