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Giornale Italiano di Dermatologia e Venereologia 2007 October;142(5):437-48


language: English

Macrophages and dendritic cells as accessory innate immunocytes in psoriasis: review of immunophenotypes and perspective of in situ identification by topoproteome analysis using Multi Epitope Ligand Cartography

Bonnekoh B. 1*, Böckelmann R. 1, 2*, Pommer A. J. 2*, Hofmeister H. 2, Philipsen L. 3, Gollnick H. 1

1 Clinic for Dermatology and Venereology Otto-von-Guericke University, Magdeburg, Germany 2 SkinSysTec GmbH, Magdeburg, Germany 3 MelTec GmbH & Co. KG, Magdeburg, Germany


Today the pathogenesis of psoriasis is recognized to be a complex and subtle interplay between diverse types of lymphocytes and innate immunity-related accessory cells, capable of antigen presentation resulting in keratinocyte hyperproliferation. These molecular and cellular events take place in a skin microenvironment, which also with regard to activated endothelial cells resembles transformation into secondary cutaneous lymphoid tissue. It is a matter of current scientific debate if these interactions may be induced and sustained by the existence of psoriasis-relevant autoantigens such as keratin 17 peptides or cyclic citrullinated peptides. Inflammatory cell types being decisive for psoriasis include Th1, Tc1, NKT, T-reg, Th17 cells, myeloid as well as lymphoid dendritic cells and their precursors at various maturation and activation stages. It is the scope of the current review to compile data upon the immuno-phenotype and -function of the latter group of professional antigen presenting cells (APC) and precursors. This comprises monocytes, macrophages/interstitial/dermal dendritic cells (dendrocytes), Langerhans cells, inflammatory dendritic epidermal cells, TNF/iNOS-producing (Tip) cells and plasmacytoid dendritic cells. Psoriasis-typical type 1 reactions driven by interferon-γ and TNF-α are assumed to be orchestrated by partly dendritic cell-derived IL-23 as a master cytokine and most promising therapeutic target. In this context the breakthrough technology of Multi Epitope Ligand Cartography (MELC) is a highly advanced immunofluorescence microscopy that allows the detection of up to at least 100 epitopes in a single skin section. Pixel-precise overlay and biomathematical postprocessing of fluorescence images enable the in situ histotopographic analysis of epitope collocations in terms of topoproteomics. Employing MELC technology we have recently shown that in psoriasis plaque due to 12 weeks of successful efalizumab treatment the co-stimulatory activity mediated via CD11a was substantially reduced in relation to CD1a+ Langerhans cells and CD68+ macrophages/dermal dendritic cells.

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