Details

Autor(en) / Beteiligte

• Pflanz, Stefan
• Hibbert, Linda
• Mattson, Jeanine
• Rosales, Rency
• Vaisberg, Elena
• Bazan, J. Fernando
• Phillips, Joseph H
• McClanahan, Terrill K
• de Waal Malefyt, Rene
• Kastelein, Robert A

Titel

WSX-1 and Glycoprotein 130 Constitute a Signal-Transducing Receptor for IL-27

Ist Teil von

• The Journal of immunology (1950), 2004-02, Vol.172 (4), p.2225-2231

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• The recently discovered cytokine IL-27 belongs to the IL-6/IL-12 family of cytokines and induced proliferation of naive CD4(+) T cells and the generation of a Th1-type adaptive immune response. Although binding of IL-27 to the cytokine receptor WSX-1 was demonstrated, this interaction proved insufficient to mediate cellular effects. Hence, IL-27 was believed to form a heteromeric signaling receptor complex with WSX-1 and another, yet to be identified, cytokine receptor subunit. In this study, we describe that WSX-1 together with gp130 constitutes a functional signal-transducing receptor for IL-27. We show that neither of the two subunits itself is sufficient to mediate IL-27-induced signal transduction, but that the combination of both is required for this event. Expression analysis of WSX-1 and gp130 by quantitative PCR suggests that IL-27 might have a variety of cellular targets besides naive CD4(+) T cells: we demonstrate gene induction of a subset of inflammatory cytokines in primary human mast cells and monocytes in response to IL-27 stimulation. Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4(+) T cells, it also directly acts on cells of the innate immune system.