title: The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity.
abstract: Interleukin (IL)-27 is a multifaceted heterodimeric cytokine with pronounced pro- and anti-inflammatory as well as immunoregulatory functions. It consists of the two subunits p28/IL-30 and Epstein Bar virus-induced protein 3 (EBI3). EBI3 functions as a soluble α-receptor, and IL-27 can therefore directly activate its target cells through a heterodimer of glycoprotein 130 (gp130) and WSX-1. Being a heterodimeric cytokine that signals through gp130, IL-27 is either grouped into the IL-6 or the IL-12 family of cytokines. Originally identified as an IL-12-like cytokine that induces proliferation of CD4+ T cells and production of IFN-γ more than ten years ago, subsequent research revealed a much broader role of IL-27 in inflammation, cancer development and regulation and differentiation of immune cells. In this review, we summarize the current biochemical and molecular knowledge about the signal transduction of IL-27. Based on this, we highlight functional overlaps and plasticity with other cytokines and cytokine receptors of the IL-6/IL-12 superfamily, and describe the important role of IL-27 with regard to the differentiation of T cells, infections and cancer development. We further discuss IL-27 as a therapeutic target and how specific blockade of this cytokine could be achieved.
authors.affiliation: Institute of Biochemistry, Kiel University, Olshausenstrasse 40, Kiel 24098, Germany.
authors.forename: Samadhi
authors.initials: S
authors.lastname: Aparicio-Siegmund
authors.affiliation: Institute of Biochemistry, Kiel University, Olshausenstrasse 40, Kiel 24098, Germany. Electronic address: cgarbers@biochem.uni-kiel.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D050822:Cytokine Receptor gp130 / Q000276:immunology; D006801:Humans; D007239:Infections / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007378:Interleukins / Q000276:immunology*; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D018123:Receptors, Interleukin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C097732:EBI3 protein, human; C112441:IL27RA protein, human; C494199:IL6ST protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D018123:Receptors, Interleukin; D050822:Cytokine Receptor gp130
keywords: EBI3; Interleukin-27; WSX-1; gp130; p28