Abstract

In this study the expression of the co-stimulatory molecules ILA receptor (ILA, "induced by lymphocyte activation", CD137 in humans and 4-1BB in mice) from the TNF receptor family and ICOS receptor (ICOS, "inducible co-stimulator", CD278) from the CD28 receptor family have been studied for the first time in psoriasis vulgaris in vivo. Skin from 5 healthy subjects and both lesional and non-lesional skin from 5 psoriasis patients have been studied applying immunohistochemical staining and light microscopy as well as double-fluorescence staining and confocal laser microscopy. Neither the ILA nor the ICOS receptor was found in the skin of healthy subjects, but both were positive in lesional and interestingly also in non-lesional skin of psoriasis patients. Concerning the cellular source we found a significant upregulation of ILA receptor on mast cells in both lesional and non-lesional skin of psoriasis patients compared with healthy subjects. Expression of the ILA receptor by human mast cells in vivo could be shown for the first time. Expression of the ILA receptor was also found on T cells in psoriatic skin, but there was no significant difference between T cells from non-lesional and lesional skin of psoriasis patients. ICOS receptor was not expressed by mast cells, T cells and dendritic cells. It was however expressed by macrophages in psoriatic skin. ILA and ICOS ligands showed an equally strong constitutional expression both in skin of healthy subjects and in non-lesional and lesional skin of psoriasis patients. Therefore activation of these ligand systems seems not to play a central role in the immunopathogenesis of psoriasis in contrast to ILA and ICOS receptor. While the ligands are expressed constitutionally, activation of the ILA and ICOS receptor could result from a dysregulation of negative feedback mechanisms within these costimulatory systems and could be involved in the immunopathogenesis of psoriasis. The potential for cell activation of mast cells which strongly express the ILA receptor in non-lesional psoriatic skin could play a causative role in the well known excitability of non-lesional skin of psoriasis patients. This may also explain the so called Koebner s phenomenon in psoriasis. We identified mast cells as the predominant cell expressing the ILA receptor in both non-lesional and lesional psoriatic skin. These results suggest a central role of ILA receptor expressing mast cells in cell-cell-interactions initiating the development of psoriasis lesions.

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