title: Microarray analyses demonstrate the involvement of type I interferons in psoriasiform pathology development in D6-deficient mice.
abstract: The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.
authors.affiliation: From the Chemokine Research Group, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Baldwin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pallas
authors.forename: Vicky
authors.initials: V
authors.lastname: King
authors.forename: Thomas
authors.initials: T
authors.lastname: Jamieson
authors.forename: Clive S
authors.initials: CS
authors.lastname: McKimmie
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: José M
authors.initials: JM
authors.lastname: Carballido
authors.forename: Marcus
authors.initials: M
authors.lastname: Jaritz
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010703:Phorbol Esters / Q000633:toxicity; D011565:Psoriasis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054447:Receptors, CCR10 / Q000235:genetics*; D014158:Transcription, Genetic; D000097628:Chemokine Receptor D6
chemical_list: D007370:Interferon Type I; D010703:Phorbol Esters; D054447:Receptors, CCR10; D000097628:Chemokine Receptor D6
keywords: Chemokines; Cytokines/Interferon; Inflammation; Mouse; Psoriasis