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Immunity. 2012 Jun 29;36(6):1017-30. doi: 10.1016/j.immuni.2012.03.024. Epub 2012 Jun 21.

Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1.

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1
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. hiraharak@mail.nih.gov

Abstract

Interleukin-27 (IL-27) is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naive T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription 1 (STAT1)-dependent manner. When cocultured with naive CD4(+) T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, coadministration of naive TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4(+) T cells can restrict differentiation of Th17 cells in trans.

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PMID:
22726954
PMCID:
PMC3785111
DOI:
10.1016/j.immuni.2012.03.024
[Indexed for MEDLINE]
Free PMC Article

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