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 ORCID: https://orcid.org/0000-0002-5817-3153, O'Hara, Aisling C., Chen, Yi, Jones, Michael L., Saris, Christiaan J. M., Rose-John, Stefan, Cua, Daniel J., Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711, 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:	20 Oct 2022 08:59
URI:	https://orca.cardiff.ac.uk/id/eprint/30284

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