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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

274 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 languageEnglish
Pages (from-to)1054-1063
Number of pages10
JournalNature Immunology
Volume14
Issue number10
DOIs
StatePublished - 2013
Externally publishedYes

Funding

FundersFunder number
National Institutes of HealthAI075285, AI093903
National Institutes of Health
National Cancer InstituteR21CA164970
National Cancer Institute
National Multiple Sclerosis SocietyRG4111A1
National Multiple Sclerosis Society

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