Document Detail


CD56brightCD16(-) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation.
MedLine Citation:
PMID:  16323244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Chiara Ottaviani; Francesca Nasorri; Chiara Bedini; Ornella de Pità; Giampiero Girolomoni; Andrea Cavani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  36     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-03     Completed Date:  2006-02-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  118-28     Citation Subset:  IM    
Affiliation:
Laboratory of Immunology and Allergology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD56 / immunology,  metabolism
Chemokine CCL5
Chemokine CXCL10
Chemokines, CC / immunology*,  metabolism
Chemokines, CXC / immunology*,  metabolism
Chemotaxis, Leukocyte / immunology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunohistochemistry
Inflammation / immunology
Keratinocytes / immunology
Killer Cells, Natural / immunology*
Psoriasis / immunology*
Receptors, IgG / immunology,  metabolism
Skin / immunology,  pathology
Chemical
Reg. No./Substance:
0/Antigens, CD56; 0/CCL5 protein, human; 0/Chemokine CCL5; 0/Chemokine CXCL10; 0/Chemokines, CC; 0/Chemokines, CXC; 0/Receptors, IgG

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