Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells
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- 13 August 2006
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 7 (9) , 929-936
- https://doi.org/10.1038/ni1375
Abstract
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-27Rα) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27Rα-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-β. This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon-γ. 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.Keywords
This publication has 45 references indexed in Scilit:
- Selective regulatory function of Socs3 in the formation of IL-17-secreting T cellsProceedings of the National Academy of Sciences, 2006
- Transforming growth factor-β induces development of the TH17 lineageNature, 2006
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Nature Immunology, 2005
- Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesNature Immunology, 2005
- IL-23 drives a pathogenic T cell population that induces autoimmune inflammationThe Journal of Experimental Medicine, 2005
- Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important for Generation of an Optimal Polymorphonuclear Response againstToxoplasma gondiiInfectionInfection and Immunity, 2005
- Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brainNature, 2003
- Granulocyte Macrophage Colony-Stimulating FactorThe Journal of Experimental Medicine, 2001
- Cloning and Characterization of a Novel Class I Cytokine ReceptorBiochemical and Biophysical Research Communications, 1998