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

• Published in: Immunity (Cambridge, Mass.) Vol. 36; no. 6; pp. 1017 - 1030
• Main Authors: Hirahara, Kiyoshi, Ghoreschi, Kamran, Yang, Xiang-Ping, Takahashi, Hayato, Laurence, Arian, Vahedi, Golnaz, Sciumè, Giuseppe, Hall, Aisling O'Hara, Dupont, Christopher D., Francisco, Loise M., Chen, Qian, Tanaka, Masao, Kanno, Yuka, Sun, Hong-Wei, Sharpe, Arlene H., Hunter, Christopher A., O'Shea, John J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29-06-2012; Elsevier Limited
• Subjects: Animals; Apoptosis; 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; Cysts; Cytokines; Design; Encephalomyelitis, Autoimmune, Experimental - etiology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Experiments; Flow cytometry; Forkhead Transcription Factors - deficiency; Gene expression; 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; Pathology; Phosphorylation; Receptors, Cytokine - deficiency; Rodents; Scholarships & fellowships; Software; T cell receptors; 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.03.024

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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► 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