title: Psoriasis in humans is associated with down-regulation of galectins in dendritic cells.
abstract: We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, expression of galectins was analysed by RT-PCR in skin samples and on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry. In the skin of healthy donors, galectin-1, -3 and -9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at the mRNA and protein levels, in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of Th1/Th17 cytokines. The analysis of galectin-1 expression showed that this protein was down-regulated in Langerhans cells and dermal dendritic cells as well as in peripheral blood CD11c(+) DCs from psoriasis patients. Expression of galectin-1 correlated with IL-17 and IL-10 expression and with the psoriasis area and index activity. Addition of galectin-1 to co-cultures of human monocyte-derived dendritic cells with autologous T lymphocytes from psoriasis patients attenuated the Th1 response. Conversely, blockade of galectin binding increased IFNγ production and inhibited IL-10 secretion in co-cultures of monocyte-derived dendritic cells with CD4(+) T cells. Our results suggest a model in which galectin-1 down-regulation contributes to the exacerbation of the Th1/Th17 effector response in psoriasis patients.
authors.affiliation: Immunology Department, Hospital de la Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: H
authors.initials: H
authors.lastname: de la Fuente
authors.forename: Silvia
authors.initials: S
authors.lastname: Perez-Gala
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Cruz-Adalia
authors.forename: Danay
authors.initials: D
authors.lastname: Cibrian
authors.forename: Silvia
authors.initials: S
authors.lastname: Sanchez-Cuellar
authors.forename: Esteban
authors.initials: E
authors.lastname: Dauden
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Amaro
authors.initials: A
authors.lastname: García-Diez
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanchez-Madrid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D037161:Galectins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C508609:IL10 protein, human; C445499:LGALS1 protein, human; C105032:LGALS9 protein, human; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma