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

• DOI: 10.1016/j.immuni.2012.03.024
• Publication Date: 2012-06-21T09:45:11Z
• Authors: Kiyoshi Hirahara; Kamran Ghoreschi; Xiang-Ping Yang; Hayato Takahashi; Arian Laurence; Golnaz Vahedi; Giuseppe Sciumè; Aisling O'Hara Hall; Christopher D. Du...; Loise M. Francisco; Qian Chen; Masao Tanaka; Yuka Kanno; Hong-Wei Sun; Arlene H. Sharpe; Christopher A. Hu...; John J. O'Shea
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; Encephalomyelitis, Autoimmune, Experimental; Interleukin-6; Interleukins; Immunology; Interleukin-17; Interleukin-1beta; Cell Differentiation; Forkhead Transcription Factors; Mice, Transgenic; Bystander Effect; Interleukin-23; B7-H1 Antigen; 3. Good health; Mice, Inbred C57BL; Minor Histocompatibility Antigens; Interferon-gamma; Mice; Infectious Diseases; Gene Expression Regulation; Immunology and Allergy; Animals; Myelin Proteins; Animals; Antigens, CD274; Bystander Effect; CD4-Positive T-Lymphocytes; Cell Differentiation; Encephalomyelitis, Autoimmune, Experimental; Forkhead Transcription Factors; Gene Expression Regulation; Interferon-gamma; Interleukin-17; Interleukin-1beta; Interleukin-23; Interleukin-6; Interleukins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Minor Histocompatibility Antigens; Myelin Proteins; Myelin-Oligodendrocyte Glycoprotein; Receptors, Cytokine; T-Lymphocyte Subsets; Th17 Cells; Transforming Growth Factor beta; Immunology and Allergy; Infectious Diseases; Immunology

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.