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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2012-06, Vol.36 (6), p.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: Article
• Language: English
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.03.024

Interleukin (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 naïve T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)1-dependent manner. When co-cultured with naïve 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 , co-administration of naïve 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 .