@article{53b595a60714420ea8c6df4242a29ced,
title = "The composition and signaling of the IL-35 receptor are unconventional",
abstract = "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.",
author = "Collison, {Lauren W.} and Delgoffe, {Greg M.} and Guy, {Clifford S.} and Vignali, {Kate M.} and Vandana Chaturvedi and Delisa Fairweather and Satoskar, {Abhay R.} and Garcia, {K. Christopher} and Hunter, {Christopher A.} and Drake, {Charles G.} and Murray, {Peter J.} and Vignali, {Dario A.A.}",
note = "Funding Information: We thank D. Fairweather and J.A. Frisancho (Johns Hopkins University) for spleens and lymph nodes from Il12rb1−/− mice; M. Karin and S. Grivennikov (University of California at San Diego) for Il6st∆T mice; C. Hunter and J. Stumhofer (University of Pennsylvania) for Il27ra−/− mice; A. Satoskar and P. Reville (Ohio State University) for Stat1−/− mice; C. Drake and H.R. Yen (Johns Hopkins University) for Stat3∆T mice; R. McEver (University of Oklahoma Health Sciences Center) for mice used to establish the colony of CD4cre × Il6stfl/fl mice at St. Jude Children{\textquoteright}s Research Hospital; M.J. Turk (Dartmouth College) for B16-F10 melanoma; J.A. Frisancho, S. Grivennikov, M. Karin, J. Stumhofer, P. Reville and H.R. Yen for assistance with the collection and shipping of spleens and lymph nodes; J. Partridge and P. Brindle for assistance in designing ChIP experiments; K. Forbes, A. Castellaw and A. Krause for the maintenance, breeding and genotyping of mouse colonies; R. Cross, G. Lennon and S. Morgan for flow cytometry; the staff of the Shared Animal Resource Center at St. Jude Children{\textquoteright}s Research Hospital for the animal husbandry; and the Hartwell Center for Biotechnology and Bioinformatics at St. Jude Children{\textquoteright}s Research Hospital for the synthesis of real-time PCR primers and probes. Supported by the US National Institutes of Health (R01 AI091977 to D.A.A.V. and F32 AI072816 to L.W.C.), NovoNordisk (D.A.A.V.), the National Cancer Institute Comprehensive Cancer Center (CA21765 to D.A.A.V.) and the American Lebanese Syrian Associated Charities (D.A.A.V.).",
year = "2012",
month = mar,
doi = "10.1038/ni.2227",
language = "English (US)",
volume = "13",
pages = "290--299",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "3",
}