engleski

The role of TNF superfamily cytokines TRAIL and TWEAK in psoriasis

Psoriasis is a common, chronic skin disorder characterized by altered growth and differentiation of keratinocytes and deregulated immune response. Recent studies as well as the use of cytokine-targeted biologic therapy highlight the importance of complex cytokine network in the genesis and maintenance of psoriatic lesions. Tumour-necrosis factor (TNF)- related apoptosis-inducing ligand (TRAIL) and TNF-like weak inducer of apoptosis (TWEAK) are relatively new members of the TNF superfamily of ligands that have emerged as cytokines that are strongly implicated in the pathogenesis of a variety of inflammatory disorders and autoimmune diseases, although there is sparse data on their role in immunodermatology. We present our recent investigations on the expression and possible roles of these two cytokines and their receptors in the pathogenesis of psoriatic lesions. According to our data based on immunohistochemical and double-immunofluorescent analyses, TRAIL is abundantly present in lesional psoriatic skin, both in the hyperplastic epidermis as well as different populations of immune cells comprising the inflammatory infiltrate. Among the complex receptor system of TRAIL receptors, DR5 and DcR2 seem to be most important for TRAILmediated responses in psoriasis. On the contrary, TWEAK seems to be down-regulated in psoriatic epidermis and it might be an early indicator of disturbed keratinocytes’ differentiation in psoriasis, as evidenced by PCNA and cytokeratin-10 co- localisation analysis. We conclude that future studies with the manipulation of these two TNF-related cytokines in animal models of psoriasis might provide important advances in understanding the pathogenesis of this complex disease.

Psoriasis; TRAIL; TWEAK

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