Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system

Jason 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 Hunter¹

¹  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.

Studies have focused on the events that influence the development of interleukin 17 (IL-17)–producing T helper cells (T_H-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T_H-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 T_H-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 T_H-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.

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