Nature immunology, 2012-03, Vol.13 (3), p.290-299
2012
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- Autor(en) / Beteiligte
- Titel
- The composition and signaling of the IL-35 receptor are unconventional
- Ist Teil von
- Nature immunology, 2012-03, Vol.13 (3), p.290-299
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/ni.2227Titel-ID: cdi_pubmed_primary_22306691
- Format
- –
- Schlagworte
- Animals, Cytokine Receptor gp130 - immunology, Interleukins - immunology, Mice, Mice, Knockout, Models, Molecular, Protein Multimerization, Protein Structure, Quaternary, Receptors, Interleukin - chemistry, Receptors, Interleukin - deficiency, Receptors, Interleukin - immunology, Receptors, Interleukin - metabolism, Receptors, Interleukin-1 - chemistry, Receptors, Interleukin-1 - deficiency, Receptors, Interleukin-1 - immunology, Receptors, Interleukin-1 - metabolism, Receptors, Interleukin-12 - immunology, Signal Transduction, STAT1 Transcription Factor - immunology, STAT4 Transcription Factor - immunology