title: CD56brightCD16(-) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation.
abstract: Psoriasis is an immune-mediated skin disease characterized by lymphocytic infiltration and altered keratinocyte differentiation. Using immunohistochemical techniques we found that the cellular infiltrate in acute psoriatic plaques includes 5-8% CD3(-)CD56(+) natural killer (NK) cells, mostly localized in the mid and papillary dermis. NK lymphocytes isolated from punch biopsy specimens of psoriatic plaques showed a CD56(bright)CD16(-)CD158b(-) phenotype, failed to express the skin homing cutaneous lymphocyte-associated antigen and released abundant IFN-gamma upon stimulation. Supernatants from psoriatic NK cells induced MHC class II and ICAM-1 expression and release of CXCL10 and CCL5 by cultured psoriatic keratinocytes. Skin NK cells expressed high levels of the chemokines receptors CXCR3 and CCR5, intermediate amounts of CXCR1, CCR6 and CCR8, and low levels of CCR1, CCR2, CCR4, CCR7 and CX3CR1. In addition, they promptly migrated in vitro toward CXCL10, CCL5, supernatants of IFN-gamma-activated psoriatic keratinocytes and, to a lower extent, CCL20 and CCL4. In contrast, they failed to migrate toward CXCL8, CCL1, CCL2, CCL3, CCL17, CCL19 and CX3CL1. Taken together, our results implicate NK lymphocytes as newly identified protagonists in the pathogenesis of psoriasis. Their distinctive homing properties should be taken into account in the design of specific therapy aimed at blocking pathogenic cell accumulation in the skin.
authors.affiliation: Laboratory of Immunology and Allergology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ottaviani
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Chiara
authors.initials: C
authors.lastname: Bedini
authors.forename: Ornella
authors.initials: O
authors.lastname: de Pità
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000276:immunology* / Q000378:metabolism; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: C483024:CCL5 protein, human; D019002:CD56 Antigen; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017452:Receptors, IgG