The composition and signaling of the IL-35 receptor are unconventional.
Nat Immunol
; 13(3): 290-9, 2012 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-22306691
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-12Rß2 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Receptores de Interleucina-1
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Receptores de Interleucina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article