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Nat Immunol. 2010 Dec;11(12):1119-26. doi: 10.1038/ni.1957. Epub 2010 Nov 7.

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

Author information

1
University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.

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.

PMID:
21057510
PMCID:
PMC3059498
DOI:
10.1038/ni.1957
[Indexed for MEDLINE]
Free PMC Article

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