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The composition and signaling of the IL-35 receptor are unconventional
Open accessAbstract
Interleukin 35 (IL-35) belongs to the IL-12 family of heterodimeric cytokines but has a distinct functional profile. IL-35 suppresses T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells (iTr35 cells). Here we found that IL-35 signaled through a unique heterodimer of receptor chains IL-12Rβ2 and gp130 or homodimers of each chain. Conventional T cells were sensitive to IL-35-mediated suppression in the absence of one receptor chain but not both receptor chains, whereas signaling through both chains was required for IL-35 expression and conversion into iTr35 cells. Signaling through the IL-35 receptor required the transcription factors STAT1 and STAT4, which formed a unique heterodimer that bound to distinct sites in the promoters of the genes encoding the IL-12 subunits p35 and Ebi3. This unconventional mode of signaling, distinct from that of other members of the IL-12 family, may broaden the spectrum and specificity of IL-35-mediated suppression.
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Awasthi, A., Carrier, Y., Peron, J. P. S., Bettelli, E., Kamanaka, M., Flavell, R. A., Kuchroo, V. K., Oukka, M., & Weiner, H. L. (2007) · Nature Immunology · doi:10.1038/ni1541 · Cited by 804
Primary Biliary Cirrhosis Associated with HLA, IL12A, and IL12RB2 Variants
Hirschfield, G. M., Liu, X., Xu, C., Lu, Y., Xie, G., Lu, Y., Gu, X., Walker, E. J., Jing, K., Juran, B. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810440 · Cited by 594
Fitzgerald, D. C., Zhang, G.-X., El-Behi, M., Fonseca-Kelly, Z., Li, H., Yu, S., Saris, C. J. M., Gran, B., Ciric, B., & Rostami, A. (2007) · Nature Immunology · doi:10.1038/ni1540 · Cited by 529
DNA Binding Specificity of Different STAT Proteins
Ehret, G. B., Reichenbach, P., Schindler, U., Horvath, C. M., Fritz, S., Nabholz, M., & Bucher, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m001748200 · Cited by 369
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Jones, S. A., & Jenkins, B. J. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0066-7 · Cited by 1,102
Interleukin-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
Pleiotropy and specificity: insights from the interleukin 6 family of cytokines
Murakami, M., Kamimura, D., & Hirano, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.027 · Cited by 533
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-citationHistorical overview of the interleukin-6 family cytokine
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Metadata
- Authors
- Collison, L. W., Delgoffe, G. M., Guy, C. S., Vignali, K. M., Chaturvedi, V., Fairweather, D., Satoskar, A. R., Garcia, K. C., Hunter, C. A., Drake, C. G., Murray, P. J., & Vignali, D. A. A.
- Venue
- Nature Immunology
- Published
- 2012-02-05
- Volume
- 13
- Issue
- 3
- Pages
- 290-299
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2056138805
- Cited by
- 450
- References
- 4
- FWCI
- 14.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Collison, L. W., Delgoffe, G. M., Guy, C. S., Vignali, K. M., Chaturvedi, V., Fairweather, D., Satoskar, A. R., Garcia, K. C., Hunter, C. A., Drake, C. G., Murray, P. J., & Vignali, D. A. A. (2012). The composition and signaling of the IL-35 receptor are unconventional. Nature Immunology. https://doi.org/10.1038/ni.2227
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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