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Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27–stimulated T cells

A Corrigendum to this article was published on 01 January 2008

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Abstract

Excessive inflammation occurs during infection and autoimmunity in mice lacking the α-subunit of the interleukin 27 (IL-27) receptor. The molecular mechanisms underlying this increased inflammation are incompletely understood. Here we report that IL-27 upregulated IL-10 in effector T cells that produced interferon-γ and expressed the transcription factor T-bet but did not express the transcription factor Foxp3. These IFN-γ+T-bet+Foxp3 cells resembled effector T cells that have been identified as the main source of host-protective IL-10 during inflammation. IL-27-induced production of IL-10 was associated with less secretion of IL-17, and exogenous IL-27 reduced the severity of adoptively transferred experimental autoimmune encephalomyelitis by a mechanism dependent on IL-10. Our data show that IL-27-induced production of IL-10 by effector T cells contributes to the immunomodulatory function of IL-27.

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Figure 1: IL-27 upregulates the production of IL-10 by activated T cells.
Figure 2: The cellular source of IL-27-induced IL-10 is IFN-γ+T-bet+ effector T cells.
Figure 3: IL-27-induced production of IL-10 requires IL-27R signaling in T cells but is enhanced by non–T cells in a contact-independent way.
Figure 4: STAT1 mediates the upregulation of IL-10 by IL-27.
Figure 5: IL-27-induced IL-10 suppresses the production of IL-17 but not IL-2.
Figure 6: IL-10 mediates the suppressive effect of exogenous IL-27 on EAE induced by adoptive transfer.

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Change history

  • 28 November 2007

    In the version of this article initially published, the initials for the seventh author are incorrect. The correct author name is Christiaan J M Saris. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank K.S. Shindler and K. Regan for critical review of this manuscript, and P.-H. Lee for technical assistance. Supported by the National Institutes of Health (5RO1NS0467892 and 5RO1AI061818), the National Multiple Sclerosis Society (F66801), the Commonwealth of Pennsylvania Department of Health (A75201 to A.R.), the Groff Foundation (F65001 to A.R.) and by a postdoctoral fellowship to D.C.F. from the National Multiple Sclerosis Society (FG1645-A-1).

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D.C.F. was involved in all aspects of the study and wrote the manuscript; G.-X.Z., M.E.-B., B.G., B.C. and A.R. contributed to conceptual and experimental design; M.E.-B. and Z.F.-K. contributed to in vitro and in vivo experiments; H.L. and S.Y. contributed to in vivo experiments; C.J.S. contributed to Il27ra−/− studies; all authors critically reviewed and contributed to the manuscript; and A.R. directed and supervised all aspects of the study and the writing and editing of the manuscript.

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Correspondence to Abdolmohamad Rostami.

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Fitzgerald, D., Zhang, GX., El-Behi, M. et al. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27–stimulated T cells. Nat Immunol 8, 1372–1379 (2007). https://doi.org/10.1038/ni1540

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