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A role for IL-27p28 as an antagonist of gp130-mediated signaling

Stumhofer, Jason S., Tait, Elia D., III, William J. Quinn, Hosken, Nancy, Spudy, Björn, Goenka, Radhika, Fielding, Ceri Alan, O'Hara, Aisling C., Chen, Yi, Jones, Michael L., Saris, Christiaan J. M., Rose-John, Stefan, Cua, Daniel J., Jones, Simon Arnett, Elloso, Merle M., Grötzinger, Joachim, Cancro, Michael P., Levin, Steven D. and Hunter, Christopher A. 2010. A role for IL-27p28 as an antagonist of gp130-mediated signaling. Nature Immunology 11 (12) , pp. 1119-1126. 10.1038/ni.1957

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Abstract

The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique functions. Here we show that IL-27p28, independently of EBI3, antagonized cytokine signaling through gp130 and IL-6-mediated production of IL-17 and IL-10. Similarly, the ability to generate antibody responses was dependent on the activity of gp130-signaling cytokines. Mice transgenic for expression of IL-27p28 showed a substantial defect in the formation of germinal centers and antibody production. Thus, IL-27p28, as a natural antagonist of gp130-mediated signaling, may be useful as a therapeutic for managing inflammation mediated by cytokines that signal through gp130.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: Nature Publishing Group
ISSN: 1529-2908
Last Modified: 04 Jun 2017 03:59
URI: http://orca.cf.ac.uk/id/eprint/30284

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