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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / deficiency
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / physiology*
  • Bystander Effect
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Forkhead Transcription Factors / deficiency
  • Gene Expression Regulation / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-17 / physiology
  • Interleukin-1beta / pharmacology
  • Interleukin-23 / pharmacology
  • Interleukin-6 / pharmacology
  • Interleukins / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Myelin Proteins / immunology
  • Myelin Proteins / toxicity
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Cytokine / deficiency
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • Th17 Cells / cytology
  • Th17 Cells / drug effects*
  • Th17 Cells / metabolism
  • Th17 Cells / transplantation
  • Transforming Growth Factor beta / pharmacology

Substances

  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Ebi3 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • IL27 protein, human
  • Il27 protein, mouse
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • MOG protein, human
  • Minor Histocompatibility Antigens
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Cytokine
  • Transforming Growth Factor beta
  • Interferon-gamma