Immunity (Cambridge, Mass.), 2012-06, Vol.36 (6), p.1017-1030
2012
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- Autor(en) / Beteiligte
- Titel
- Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1
- Ist Teil von
- Immunity (Cambridge, Mass.), 2012-06, Vol.36 (6), p.1017-1030
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] ► 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
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2012.03.024Titel-ID: cdi_proquest_miscellaneous_1113219268
- Format
- –
- Schlagworte
- 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