Abstract
Psoriasis is a type I interferon-driven T cell-mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15(+) neutrophils and CD123(+)/BDCA-2(+)/ChemR23(+) pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development.
MeSH Terms
Adult
Antibodies, Monoclonal/immunology,pharmacology
Antigens, CD/metabolism
Blotting, Western
CD8-Positive T-Lymphocytes/cytology,drug effects,metabolism
Calcitriol/pharmacology
Cells, Cultured
Chemokine CXCL10/genetics,metabolism
Chemokines/genetics,metabolism
Chemotaxis, Leukocyte/drug effects,physiology
Culture Media, Conditioned/pharmacology
Dendritic Cells/cytology,metabolism
Dermatitis, Atopic/genetics,metabolism,pathology
Extracellular Signal-Regulated MAP Kinases/metabolism
Fibroblasts/cytology,drug effects,metabolism
Gene Expression/drug effects
Humans/metabolism
Intercellular Adhesion Molecule-1/metabolism
Intercellular Signaling Peptides and Proteins
Lectins, C-Type/genetics,metabolism
Membrane Glycoproteins/genetics,metabolism
Neutrophils/cytology,drug effects,metabolism
Psoriasis/genetics,metabolism,pathology
Receptors, Chemokine/genetics,immunology,metabolism
Receptors, Immunologic/genetics,metabolism
Reverse Transcriptase Polymerase Chain Reaction
Skin/metabolism,pathology
Tretinoin/pharmacology
Chemicals
Antibodies, Monoclonal
Antigens, CD
CLEC4C protein, human
CMKLR1 protein, human
CXCL10 protein, human
Chemokine CXCL10
Chemokines
Culture Media, Conditioned
Intercellular Signaling Peptides and Proteins
Lectins, C-Type
Membrane Glycoproteins
RARRES2 protein, human
Receptors, Chemokine
Receptors, Immunologic
Intercellular Adhesion Molecule-1
Tretinoin
Extracellular Signal-Regulated MAP Kinases
Calcitriol
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Albanesi Cristina
Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00167 Rome, Italy.
Scarponi Claudia
Pallotta Sabatino
Daniele Roberta
Bosisio Daniela
Madonna Stefania
Fortugno Paola
Gonzalvo-Feo Safiyè
Franssen Jean-Denis
Parmentier Marc
De Pità Ornella
Girolomoni Giampiero
Sozzani Silvano
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