Liječnički vjesnik, Vol. 132 No. 11-12, 2010.
Review article
THE ROLE OF PERFORIN MEDIATED CELL CYTOTOXICITY IN PSORIASIS
MARIJA KAŠTELAN
LARISA PRPIĆ MASSARI,
SANDRA PETERNEL
Abstract
Psoriasis is a common chronic inflammatory skin disease characterized by hyperproliferation and incomplete differentiation of epidermal keratinocytes as well as by inflammatory infiltrate of T-lymphocytes in dermis and epidermis. Psoriasis is nowadays also recognized as a T cell mediated disease resulting from aberrant activation of both innate and
adaptive immunity. The main effector cells in mediating psoriatic phenotype are helper CD4+ T cells and cytotoxic CD8+ T cells. Both, CD4+ and CD8+ T cells, mediate apoptosis via the release of cell granules, perforin and granzymes or by binding of ligands to their death receptors on target cells. The role of cell cytotoxicity mechanisms, particularly those mediated by perforin, in psoriasis is as yet unclear. Perforin is a pore forming molecule, located within the cytoplasm of cytotoxic T cells and natural killer cells, which enables entry of granzymes and other apoptotic molecules into the target cell in order to mediate programmed cell death. The importance of perforin-mediated cytotoxicity has been demonstrated in several autoimmune diseases and in some inflammatory skin diseases. Recent studies claimed its role in the immunopathogenesis of psoriasis as well. Accumulation of perforin-positive cells in psoriatic epidermis close to damaged keratinocytes suggests that T lymphocytes induce damage to keratinocytes by releasing cytolytic molecules. On the other hand, apoptotic keratinocytes might trigger an injury response program causing regenerative hyperplasia of epidermal keratinocytes, a hallmark of psoriasis. Progress in understanding of effector part of cell cytotoxicity in psoriatic plaque might in future enable more specific treatment of psoriatic patients by blocking selectively each of proposed cytolytic mechanisms and molecules as potential new therapeutic targets.
Keywords
Psoriasis – immunology, pathology; t-lymphocytes, cytotoxic – immunology, metabolism; Killer cells, natural – immunology, metabolism; Perforin – immunology; Pore forming cytotoxic proteins – immunology; Keratinocytes – pathology; Apoptosis; Cytotoxicity, immunologic
Hrčak ID:
221465
URI
Publication date:
31.12.2010.
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