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Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment.

Albanesi C, Scarponi C, Pallotta S, Daniele R, Bosisio D, Madonna S, Fortugno P, Gonzalvo-Feo S, Franssen JD, Parmentier M, De Pità O, Girolomoni G, Sozzani S - J. Exp. Med. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00167 Rome, Italy.

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.

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Chemerin expression in healthy and diseased skin. Immunohistochemistry was performed with an anti-chemerin mAb (red) on the following: a, LS (12 different subjects); b, nonlesional (NLS; 10 different subjects); c, normal skin from healthy donors (6 different subjects); and d, AD LS skin (5 different subjects). Bars, 20 μm. Chemerin was highly expressed in the dermis of psoriatic lesions but not in NLS psoriatic or healthy skin. Few chemerin+ cells were present in the dermis of AD LS skin. In addition, chemerin immunoreactivity was intense throughout the epidermis of healthy and NLS psoriatic skin, whereas in LS it was weak and confined to the suprabasal layer keratinocytes. The figure is representative of the results on skin biopsies obtained from all the different donors indicated.
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fig1: Chemerin expression in healthy and diseased skin. Immunohistochemistry was performed with an anti-chemerin mAb (red) on the following: a, LS (12 different subjects); b, nonlesional (NLS; 10 different subjects); c, normal skin from healthy donors (6 different subjects); and d, AD LS skin (5 different subjects). Bars, 20 μm. Chemerin was highly expressed in the dermis of psoriatic lesions but not in NLS psoriatic or healthy skin. Few chemerin+ cells were present in the dermis of AD LS skin. In addition, chemerin immunoreactivity was intense throughout the epidermis of healthy and NLS psoriatic skin, whereas in LS it was weak and confined to the suprabasal layer keratinocytes. The figure is representative of the results on skin biopsies obtained from all the different donors indicated.

Mentions: Based on previous work showing that pDC abundantly infiltrate psoriatic skin, we sought to assess chemerin presence in psoriatic plaque lesions. Chemerin expression and distribution were investigated by immunohistochemistry in both uninvolved and LS skin of psoriatic patients and, in parallel, in skin of patients affected by atopic dermatitis (AD) or healthy individuals. Skin biopsies from psoriatic lesions showed numerous chemerin+ cells localized in the dermis and scattered throughout the T cell–rich infiltrate (Fig. 1 A). In contrast, only a few chemerin immunoreactive cells were detected in the dermis of uninvolved psoriatic skin or healthy skin (Fig. 1, B and C, respectively) or in the dermis of AD lesions (Fig. 1 D). Double staining analysis revealed that the majority of chemerin+ cells were dermal cells with a fibroblast morphology coexpressing vimentin, which is a typical mesenchymal cell marker (Fig. 2, A and B). Some of the dermal chemerin+ cells also coexpressed FVIII+, which stains blood endothelial cells (∼20% of dermal vessels), and ∼5% of total chemerin+ cells expressed c-kit+, which is a mast cell marker (Fig. 2, C and D, respectively). Conversely, chemerin immunoreactivity did not colocalize with CD15+, CD3+, BDCA-2+, CD1a+, CD1b+, or CD14+ markers (Fig. 2, E and F; and not depicted). Finally, expression of chemerin immunoreactivity was also observed in the epidermal compartment of healthy or uninvolved psoriatic skin (Fig. 1, B and C). On the contrary, and in agreement with a previous study (26), LS psoriatic plaques displayed a weak chemerin expression in the epidermis that was confined to the keratinocyte suprabasal layer (Fig. 1 A).


Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment.

Albanesi C, Scarponi C, Pallotta S, Daniele R, Bosisio D, Madonna S, Fortugno P, Gonzalvo-Feo S, Franssen JD, Parmentier M, De Pità O, Girolomoni G, Sozzani S - J. Exp. Med. (2008)

Chemerin expression in healthy and diseased skin. Immunohistochemistry was performed with an anti-chemerin mAb (red) on the following: a, LS (12 different subjects); b, nonlesional (NLS; 10 different subjects); c, normal skin from healthy donors (6 different subjects); and d, AD LS skin (5 different subjects). Bars, 20 μm. Chemerin was highly expressed in the dermis of psoriatic lesions but not in NLS psoriatic or healthy skin. Few chemerin+ cells were present in the dermis of AD LS skin. In addition, chemerin immunoreactivity was intense throughout the epidermis of healthy and NLS psoriatic skin, whereas in LS it was weak and confined to the suprabasal layer keratinocytes. The figure is representative of the results on skin biopsies obtained from all the different donors indicated.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2626680&req=5

fig1: Chemerin expression in healthy and diseased skin. Immunohistochemistry was performed with an anti-chemerin mAb (red) on the following: a, LS (12 different subjects); b, nonlesional (NLS; 10 different subjects); c, normal skin from healthy donors (6 different subjects); and d, AD LS skin (5 different subjects). Bars, 20 μm. Chemerin was highly expressed in the dermis of psoriatic lesions but not in NLS psoriatic or healthy skin. Few chemerin+ cells were present in the dermis of AD LS skin. In addition, chemerin immunoreactivity was intense throughout the epidermis of healthy and NLS psoriatic skin, whereas in LS it was weak and confined to the suprabasal layer keratinocytes. The figure is representative of the results on skin biopsies obtained from all the different donors indicated.
Mentions: Based on previous work showing that pDC abundantly infiltrate psoriatic skin, we sought to assess chemerin presence in psoriatic plaque lesions. Chemerin expression and distribution were investigated by immunohistochemistry in both uninvolved and LS skin of psoriatic patients and, in parallel, in skin of patients affected by atopic dermatitis (AD) or healthy individuals. Skin biopsies from psoriatic lesions showed numerous chemerin+ cells localized in the dermis and scattered throughout the T cell–rich infiltrate (Fig. 1 A). In contrast, only a few chemerin immunoreactive cells were detected in the dermis of uninvolved psoriatic skin or healthy skin (Fig. 1, B and C, respectively) or in the dermis of AD lesions (Fig. 1 D). Double staining analysis revealed that the majority of chemerin+ cells were dermal cells with a fibroblast morphology coexpressing vimentin, which is a typical mesenchymal cell marker (Fig. 2, A and B). Some of the dermal chemerin+ cells also coexpressed FVIII+, which stains blood endothelial cells (∼20% of dermal vessels), and ∼5% of total chemerin+ cells expressed c-kit+, which is a mast cell marker (Fig. 2, C and D, respectively). Conversely, chemerin immunoreactivity did not colocalize with CD15+, CD3+, BDCA-2+, CD1a+, CD1b+, or CD14+ markers (Fig. 2, E and F; and not depicted). Finally, expression of chemerin immunoreactivity was also observed in the epidermal compartment of healthy or uninvolved psoriatic skin (Fig. 1, B and C). On the contrary, and in agreement with a previous study (26), LS psoriatic plaques displayed a weak chemerin expression in the epidermis that was confined to the keratinocyte suprabasal layer (Fig. 1 A).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00167 Rome, Italy.

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.

Show MeSH
Related in: MedlinePlus