Kastelan Marija, Massari Larisa Prpić, Peternel Sandra
Klinika za kozne i spolne bolesti, Medicinski fakultet i KBC Rijeka.
Lijec Vjesn. 2010 Nov-Dec;132(11-12):361-4.
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.
银屑病是一种常见的慢性炎症性皮肤病，其特征为表皮角质形成细胞过度增殖和不完全分化，以及真皮和表皮中T淋巴细胞的炎性浸润。如今，银屑病也被认为是一种由先天性和适应性免疫异常激活导致的T细胞介导的疾病。介导银屑病表型的主要效应细胞是辅助性CD4+ T细胞和细胞毒性CD8+ T细胞。CD4+和CD8+ T细胞均通过释放细胞颗粒、穿孔素和颗粒酶或通过配体与靶细胞上的死亡受体结合来介导细胞凋亡。细胞毒性机制，尤其是由穿孔素介导的机制，在银屑病中的作用尚不清楚。穿孔素是一种形成孔道的分子，位于细胞毒性T细胞和自然杀伤细胞的细胞质中，它能使颗粒酶和其他凋亡分子进入靶细胞，从而介导程序性细胞死亡。穿孔素介导的细胞毒性的重要性已在几种自身免疫性疾病和一些炎症性皮肤病中得到证实。最近的研究也表明其在银屑病的免疫发病机制中起作用。银屑病表皮中靠近受损角质形成细胞的穿孔素阳性细胞的积累表明，T淋巴细胞通过释放溶细胞分子诱导角质形成细胞损伤。另一方面，凋亡的角质形成细胞可能触发一种损伤反应程序，导致表皮角质形成细胞再生性增生，这是银屑病的一个标志。未来，对银屑病斑块中细胞毒性效应部分的理解取得进展，可能通过选择性阻断每种提出的溶细胞机制和分子作为潜在的新治疗靶点，实现对银屑病患者更具特异性的治疗。
