Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1.
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.
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. hiraharak@mail.nih.gov
Kiyoshi
K
Hirahara
Kamran
K
Ghoreschi
Xiang-Ping
XP
Yang
Hayato
H
Takahashi
Arian
A
Laurence
Golnaz
G
Vahedi
Giuseppe
G
Sciumè
Aisling O'Hara
AO
Hall
Christopher D
CD
Dupont
Loise M
LM
Francisco
Qian
Q
Chen
Masao
M
Tanaka
Yuka
Y
Kanno
Hong-Wei
HW
Sun
Arlene H
AH
Sharpe
Christopher A
CA
Hunter
John J
JJ
O'Shea
D000818:Animals; D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024201:Bystander Effect; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051858:Forkhead Transcription Factors / Q000172:deficiency; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D053583:Interleukin-1beta / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D009185:Myelin Proteins / Q000276:immunology / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D018121:Receptors, Cytokine / Q000172:deficiency; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C499601:Ebi3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C486767:Il27 protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; C571326:MOG protein, human; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D018121:Receptors, Cytokine; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma