The composition and signaling of the IL-35 receptor are unconventional

Lauren W. Collison, Greg M. Delgoffe, Clifford S. Guy, Kate M. Vignali, Vandana Chaturvedi, Delisa Fairweather, Abhay R. Satoskar, K. Christopher Garcia, Christopher A. Hunter, Charles G. Drake, Peter J. Murray, Dario A.A. Vignali

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)290-299
Number of pages10
JournalNature Immunology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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