title: Modulation of inflammation by interleukin-27.
abstract: A growing body of evidence suggests an essential role of the heterodimeric cytokine, IL-27, for regulating immunity. IL-27 is composed of two subunits (p28 and EBI3) and is classified as a member of the IL-12 family of cytokines. APCs have been recognized as a major cellular source of IL-27 following activation with microbial products or IFNs (types I and II). In this review, we describe the current knowledge of the implications of IL-27 during the pathogenesis of infectious and autoimmune diseases. Experimental studies have used genetically targeted IL-27RA-/- mice, EBI3-/- mice, and p28-/- mice or involved study designs with administration of bioengineered IL-27/IL-27RA homologs. Whereas many reports have described that IL-27 suppresses inflammation, we also review the current literature, suggesting promotion of inflammation by IL-27 in some settings. Recent advances have also been made in understanding the cross-talk of cleavage products of the complement system with IL-27-mediated immune responses. Additional data on IL-27 have been obtained recently by observational studies in human patients with acute and chronic inflammatory diseases. Collectively, the findings from the past decade identify IL-27 as a critical immunoregulatory cytokine, especially for T cells, whereas some controversy is fueled by results challenging the view of IL-27 as a classical silencer of inflammation.
authors.affiliation: 1.University of Michigan Medical School, 1301 Catherine Rd., Ann Arbor, MI 48109-5602, USA. pward@umich.edu.
authors.forename: Markus
authors.initials: M
authors.lastname: Bosmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*
chemical_list: C097732:EBI3 protein, human; C499601:Ebi3 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine
keywords: EBI3; IL-30; WSX-1; macrophages; p28
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