期刊
NATURE IMMUNOLOGY
卷 11, 期 12, 页码 1119-U118出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1957
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资金
- US National Institutes for Health [AI-042334, AI-054488, 1-T32-AI-055428, 2-T32-AI-007532-11]
- Abramson Cancer Center (Center for Digestive Diseases)
- State of Pennsylvania
- Deutsche Forschungsgemeinschaft (Bonn, Germany) [SFB415, B5, SFB415, B7]
- Cluster of Excellence 'Inflammation at Interfaces'
- Marie Lowe Cancer Center of the University of Pennsylvania
- Versus Arthritis [18286] Funding Source: researchfish
The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27R alpha 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.
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