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

Ivan D. Mascanfroni; Ada Yeste; Silvio M. Vieira; Evan J. Burns; Bonny Patel; Ido Sloma; Yan Wu; Lior Mayo; Rotem Ben-Hamo; Sol Efroni; Vijay K. Kuchroo; Simon C. Robson; Francisco J. Quintana

doi:10.1038/ni.2695

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

Ivan D. Mascanfroni
, Ada Yeste
, Silvio M. Vieira
, Evan J. Burns
, Bonny Patel
, Ido Sloma
, Yan Wu
, Lior Mayo
, Rotem Ben-Hamo
, Sol Efroni
, Vijay K. Kuchroo
, Simon C. Robson
, Francisco J. Quintana

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

300 Scopus citations

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 T H 1 and T H 17 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.

Original language	English
Pages (from-to)	1054-1063
Number of pages	10
Journal	Nature Immunology
Volume	14
Issue number	10
DOIs	https://doi.org/10.1038/ni.2695
State	Published - Oct 2013

Bibliographical note

Funding Information:
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.).

Funding

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.).

Funders	Funder number
National Institutes of Health	AI075285, AI093903
National Cancer Institute	R21CA164970
National Multiple Sclerosis Society	RG4111A1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/ni.2695

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Mascanfroni, I. D., Yeste, A., Vieira, S. M., Burns, E. J., Patel, B., Sloma, I., Wu, Y., Mayo, L., Ben-Hamo, R., Efroni, S., Kuchroo, V. K., Robson, S. C., & Quintana, F. J. (2013). IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nature Immunology, 14(10), 1054-1063. https://doi.org/10.1038/ni.2695

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

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 T H 1 and T H 17 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.",

author = "Mascanfroni, \{Ivan D.\} and Ada Yeste and Vieira, \{Silvio M.\} and Burns, \{Evan J.\} and Bonny Patel and Ido Sloma and Yan Wu and Lior Mayo and Rotem Ben-Hamo and Sol Efroni and Kuchroo, \{Vijay K.\} and Robson, \{Simon C.\} and Quintana, \{Francisco J.\}",

note = "Funding Information: 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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AU - Mascanfroni, Ivan D.

AU - Yeste, Ada

AU - Vieira, Silvio M.

AU - Burns, Evan J.

AU - Patel, Bonny

AU - Sloma, Ido

AU - Wu, Yan

AU - Mayo, Lior

AU - Ben-Hamo, Rotem

AU - Efroni, Sol

AU - Kuchroo, Vijay K.

AU - Robson, Simon C.

AU - Quintana, Francisco J.

N1 - Funding Information: 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.).

PY - 2013/10

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N2 - 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 T H 1 and T H 17 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.

AB - 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 T H 1 and T H 17 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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IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39

Abstract

Bibliographical note

Funding

UN SDGs

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