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

By S. Pflanz, L. Hibbert, J. Mattson, R. Rosales, E. Vaisberg, J. Bazan, J. Phillips, T. Mcclanahan, R. de Waal Malefyt, R. Kastelein. 2004

760 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Oncology

Citations in the corpus

Interleukin‐6 biology is coordinated by membrane‐bound and soluble receptors: role in inflammation and cancer (2006, background): “characterized cytokines IL-27 and IL-31 [3, 4].”
IL-17 family cytokines and the expanding diversity of effector T cell lineages. (2007, background): “The receptor for IL-27 is composed of two subunits, IL-27Rα (also called WSX-1 or TCCR), expression of which is limited to immune cells, and gp130, which is shared with several members of the IL-6 receptor family and is expressed more widely on both immune and nonimmune cells (123).”
Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. (2011, background): “…oncostatin-M Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), leukemia inhibitory factor (LIF), and the cardiotrophin-like cytokine (CLC) (10–17) (herein referred to as gp130-related cytokines) (Figure 1).”
Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. (2007, background): “Subsequent work revealed that WSX-1, an orphan type I cytokine receptor expressed by lymphocytes, partnered with gp130 to form a heterodimer required for IL-27 signaling (5).”
Interleukin-6 Family Cytokines. (2018, background): “This might have important functional consequences because a homodimeric complex of gp130 preferentially activates STAT3, whereas the heterodimeric complex of gp130 and WSX-1 rather activates STAT1, leading to a different physiologic outcome (Pflanz et al. 2004).”