Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1

SummaryInterleukin-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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (167 K)Download as PowerPoint slideHighlights► IL-27 priming of naive T cells inhibits Th17 cell differentiation in trans ► IL-27 rapidly induces gene expression in naive T cells ► IL-27 upregulates PD-L1 in naive CD4+ T cells through STAT1 ► Induction of PD-L1 by IL-27 is an important means of inhibiting IL-17