TY - JOUR
T1 - Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1
AU - Hirahara, Kiyoshi
AU - Ghoreschi, Kamran
AU - Yang, Xiang Ping
AU - Takahashi, Hayato
AU - Laurence, Arian
AU - Vahedi, Golnaz
AU - Sciumè, Giuseppe
AU - Hall, Aisling O.Hara
AU - Dupont, Christopher D.
AU - Francisco, Loise M.
AU - Chen, Qian
AU - Tanaka, Masao
AU - Kanno, Yuka
AU - Sun, Hong Wei
AU - Sharpe, Arlene H.
AU - Hunter, Christopher A.
AU - O'Shea, John J.
N1 - Funding Information:
We thank M. Pelletier (Autoimmunity Branch, NIAMS), J. Simone, J. Lay (Flow Cytometry Section, NIAMS), and the NIAMS LACU staff for their excellent technical support. We thank A. Villarino for critically reading this manuscript and providing helpful suggestions. This work was supported by the Intramural Research Programs of NIAMS, NIAID, the JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH (K.H. and H.T.), Istituto Pasteur-Fondazione Cenci-Bolognetti (G.S.), NIH R01 AI 42334 (C.A.H.), NIH R01 AI 40614 (A.H.S.), and NIH R37 AI 38310 (A.H.S.). K.H. and K.G. designed, performed, analyzed, and interpreted all the experiments and wrote the manuscript. X.-P.Y., H.T., A.L., G.S., A.O'H.H., C.D.D., L.M.F., Q.C., and M.T. helped with performing experiments. H.-W.S. and G.V. interpreted the microarray experiments and ChIP-seq data. Y.K., A.H.S., and C.A.H. contributed to the experimental design and data interpretation and made helpful suggestions. J.J.O'S. contributed to experiment design, analyzed and interpreted all acquired data, and helped to write the manuscript.
PY - 2012/6/29
Y1 - 2012/6/29
N2 - 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.
AB - 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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U2 - 10.1016/j.immuni.2012.03.024
DO - 10.1016/j.immuni.2012.03.024
M3 - Article
C2 - 22726954
AN - SCOPUS:84862981070
SN - 1074-7613
VL - 36
SP - 1017
EP - 1030
JO - Immunity
JF - Immunity
IS - 6
ER -
