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Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells
Author(s) -
de la Fuente H,
PerezGala Silvia,
Bonay Pedro,
CruzAdalia Aranzazu,
Cibrian Danay,
SanchezCuellar Silvia,
Dauden Esteban,
Fresno Manuel,
GarcíaDiez Amaro,
SanchezMadrid Francisco
Publication year - 2012
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.3996
Subject(s) - galectin , cd11c , psoriasis , dendritic cell , immunology , flow cytometry , peripheral blood mononuclear cell , biology , monocyte , medicine , immune system , in vitro , biochemistry , gene , phenotype
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. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.