title: Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset.
abstract: CCR5 expression on CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) has been reported to be crucial for limiting Th1 inflammation associated with autoimmunity and bacterial infections. We inquired whether abnormalities in chemokine receptors expressed on Tregs might be involved in the psoriatic pathogenesis. Indeed, the proportion of CCR5(+) Treg was 58.8% in healthy individuals (n=9), whereas only half as many CCR5(+) Treg cells were found in psoriatic individuals (29.1%, n=8, p<0.01). The flow-enriched control CCR5(+) Tregs consistently exceeded the suppressive capacity of unsorted Tregs in autologous MLR assays (n=5, p<0.05) showing that CCR5(+) Treg subset is a high potency regulatory T cell population. Interestingly, psoriatic CCR5(+) Treg cells exhibited significantly less migratory capacity toward CCR5 ligands MIP-1β and RANTES in vitro compared to CCR5(+) Treg controls (n=3, p<0.05). Our data demonstrate that psoriatic CCR5(+) Tregs cells are numerically-, functionally- and chemotactically-deficient compared to controls and may pose a triple impairment on the ability of psoriatic Tregs to restrain inflammation.
authors: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; The Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors: David C
authors: DC
authors: Soler
authors: Hideaki
authors: H
authors: Sugiyama
authors: Andrew B
authors: AB
authors: Young
authors: Jessica V
authors: JV
authors: Massari
authors: Thomas S
authors: TS
authors: McCormick
authors: Kevin D
authors: KD
authors: Cooper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000328:Adult; D018946:Chemokine CCL5 / Q000276:immunology; D002633:Chemotaxis; D006801:Humans; D011565:Psoriasis / Q000276:immunology*; D019713:Receptors, CCR5 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C483024:CCL5 protein, human; D018946:Chemokine CCL5; C493277:MAPKAP1 protein, human; D019713:Receptors, CCR5
keywords: Immunosuppression; Psoriasis; Regulatory T cells
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