Nature Immunology
- 7, 929 - 936 (2006)
Published online: 13 August 2006; | doi:10.1038/ni1375
Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cellsMarcel Batten1, 4, Ji Li1, 4, Sothy Yi1, Noelyn M Kljavin1, Dimitry M Danilenko2, Sophie Lucas3, James Lee1, Frederic J de Sauvage1 & Nico Ghilardi11
Department of Molecular Biology, South San Francisco, California 94080, USA. 2
Department of Pathology, Genentech, South San Francisco, California 94080, USA. 3
Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Belgium. 4
These authors contributed equally to this work.
Correspondence should be addressed to Nico Ghilardi ghilardi@gene.com Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with T helper type 1–inducing activity. However, subsequent work has demonstrated that mice deficient in IL-27 receptor (IL-27R ) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27R-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells. IL-27 acted directly on effector T cells to suppress the development of IL-17-producing T helper cells mediated by IL-6 and transforming growth factor- . This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon- . Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation.
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