title: Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis.
abstract: D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Singh
authors.forename: Vicky
authors.initials: V
authors.lastname: King
authors.forename: Helen
authors.initials: H
authors.lastname: Baldwin
authors.forename: David
authors.initials: D
authors.lastname: Burden
authors.forename: Anne
authors.initials: A
authors.lastname: Thorrat
authors.forename: Susan
authors.initials: S
authors.lastname: Holmes
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Ruairidh
authors.initials: R
authors.lastname: Nicoll
authors.forename: Kave
authors.initials: K
authors.lastname: Shams
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pallas
authors.forename: Thomas
authors.initials: T
authors.lastname: Jamieson
authors.forename: Kit Ming
authors.initials: KM
authors.lastname: Lee
authors.forename: Jose M
authors.initials: JM
authors.lastname: Carballido
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
mesh_terms: D000818:Animals; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011565:Psoriasis / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054447:Receptors, CCR10 / Q000235:genetics / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications / Q000473:pathology; D000097628:Chemokine Receptor D6
chemical_list: D012333:RNA, Messenger; D054447:Receptors, CCR10; D000097628:Chemokine Receptor D6