| First Author | Collison LW | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 3 | Pages | 290-9 |
| PubMed ID | 22306691 | Mgi Jnum | J:181328 |
| Mgi Id | MGI:5311050 | Doi | 10.1038/ni.2227 |
| Citation | Collison LW, et al. (2012) The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol 13(3):290-9 |
| abstractText | 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-12Rbeta2 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. |
