Nature Immunology
- 7, 937 - 945 (2006)
Published online: 13 August 2006; | doi:10.1038/ni1376
Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous systemJason S Stumhofer1, Arian Laurence2, Emma H Wilson1, Elaine Huang1, Cristina M Tato2, Leanne M Johnson1, Alejandro V Villarino1, Qiulong Huang3, Akihiko Yoshimura4, David Sehy3, Christiaan J M Saris5, John J O'Shea2, Lothar Hennighausen6, Matthias Ernst7 & Christopher A Hunter11
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6008, USA. 2
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Muskoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. 3
New Technologies Department, eBioscience, San Diego, California 92121, USA. 4
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 Japan. 5
Department of Inflammation Research, Amgen, Thousand Oaks, California 91320, USA. 6
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. 7
Ludwig Institute for Cancer Research, Parkville, Victoria 3050, Australia.
Correspondence should be addressed to Christopher A Hunter chunter@vet.upenn.edu Studies have focused on the events that influence the development of interleukin 17 (IL-17)–producing T helper cells (TH-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize TH-17 cell effector responses. Here we show that IL-27 receptor–deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development TH-17 cells induced by IL-6 and transforming growth factor- , which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of TH-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.
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