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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Stumhofer JS,Tait ED,Quinn WJ 3rd,Hosken N,Spudy B,Goenka R,Fielding CA,O'Hara AC,Chen Y,Jones ML,Saris CJ,Rose-John S,Cua DJ,Jones SA,Elloso MM,Grötzinger J,Cancro MP,Levin SD,Hunter CAdoi
10.1038/ni.1957subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1119-26issue
12eissn
1529-2908issn
1529-2916pii
ni.1957journal_volume
11pub_type
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