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

2012; Cell Press; Volume: 36; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2012.03.024

1097-4180

Kiyoshi Hirahara, Kamran Ghoreschi, Xiang‐Ping Yang, Hayato Takahashi, Arian Laurence, Golnaz Vahedi, Giuseppe Sciumè, Aisling O’Hara Hall, Christopher D. Dupont, Loise M. Francisco, Qian Chen, Masao Tanaka, Yuka Kanno, Hong‐Wei Sun, Arlene H. Sharpe, Christopher A. Hunter, John J. O’Shea,

Cancer Immunotherapy and Biomarkers

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.