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A role for IL-27p28 as an antagonist of gp130-mediated signaling
Open accessAbstract
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.
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Cites
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768 · cited 1×
“For example, the original characterization of Il6 −/− mice indicated that after infection with vesicular stomatitis virus and vaccinia virus, Il6 −/− mice produce five- to tenfold lower virus-neutralizing IgG titers, whereas IgM titers are similar to those of control mic”
BackgroundMcGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., & Cua, D. J. (2007) · Nature Immunology · doi:10.1038/ni1539 · Cited by 1,520
Self-citationStumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., Villarino, A. V., Huang, Q., Yoshimura, A., Sehy, D., et al. (2006) · Nature Immunology · doi:10.1038/ni1376 · Cited by 955
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Cited by
IL-6 as a keystone cytokine in health and disease
Hunter, C. A., & Jones, S. A. (2015) · Nature Immunology · doi:10.1038/ni.3153 · Cited by 2,511
Self-citationRecent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
Jones, S. A., & Jenkins, B. J. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0066-7 · Cited by 1,102
Self-citationInterleukin-35 induces regulatory B cells that suppress autoimmune disease
Wang, R.-X., Yu, C.-R., Dambuza, I. M., Mahdi, R. M., Dolinska, M. B., Sergeev, Y. V., Wingfield, P. T., Kim, S.-H., & Egwuagu, C. E. (2014) · Nature Medicine · doi:10.1038/nm.3554 · Cited by 733
The Immunobiology of the Interleukin-12 Family: Room for Discovery
Tait Wojno, E. D., Hunter, C. A., & Stumhofer, J. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.011 · Cited by 482
Self-citationIgyártó, B. Z., Haley, K., Ortner, D., Bobr, A., Gerami-Nejad, M., Edelson, B. T., Zurawski, S. M., Malissen, B., Zurawski, G., Berman, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.06.005 · Cited by 435
Metadata
- Authors
- Stumhofer, J. S., Tait, E. D., III, W. J. Q., Hosken, N., Spudy, B., Goenka, R., Fielding, C. A., O'Hara, A. C., Chen, Y., Jones, M. L., Saris, C. J. M., Rose-John, S., Cua, D. J., Jones, S. A., Elloso, M. M., Grötzinger, J., Cancro, M. P., Levin, S. D., & Hunter, C. A.
- Venue
- Nature Immunology
- Published
- 2010-11-07
- Volume
- 11
- Issue
- 12
- Pages
- 1119-1126
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2128475089
- Cited by
- 184
- References
- 4
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- green
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- Stumhofer, J. S., Tait, E. D., III, W. J. Q., Hosken, N., Spudy, B., Goenka, R., Fielding, C. A., O'Hara, A. C., Chen, Y., Jones, M. L., Saris, C. J. M., Rose-John, S., Cua, D. J., Jones, S. A., Elloso, M. M., Grötzinger, J., Cancro, M. P., Levin, S. D., & Hunter, C. A. (2010). A role for IL-27p28 as an antagonist of gp130-mediated signaling. Nature Immunology. https://doi.org/10.1038/ni.1957
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
