Apoptosis mediated by cytolytic molecules might be responsible for maintenance of psoriatic plaques.
Psoriasis is a chronic hyperproliferative skin disease characterized by keratinocyte hyperproliferation and inflammation. It is generally considered as an autoimmune disease mediated by T cells. The precise mechanism of triggering keratinocyte hyperproliferation is as yet unknown. Apoptosis seems to be important in the maintenance of skin cell homeostasis as well as in the pathogenesis of some skin diseases. We hypothesize how apoptosis mediated by cytolytic mechanisms could be involved in initiating and maintenance of psoriatic plaque. Increased keratinocyte hyperproliferation might develop as a consequence of failure to remove self-reactive T cells by apoptosis that in other way cause significant keratinocyte damage. Apoptotic keratinocytes might trigger an injury response program causing regenerative hyperplasia of epidermal keratinocytes. Another possibility is that the failure to eliminate these abnormal keratinocytes could result in the persistence of chronic inflammatory conditions constantly recruiting specific T cells. Increased epidermal thickness in psoriasis could be also explained by imbalance between the expression of pro- and anti-apoptotic proteins. Epidermal keratinocytes have the ability to produce cytolytic molecules, thus they might also have the potential to protect the epidermis from T cell-mediated damage. In conclusion, hyperproliferation of psoriatic keratinocytes might be partly due to changes in the keratinocyte expression of pro- and anti-apoptotic genes, partly to the damaged keratinocytes triggering an inappropriate wound repair response and partly by the failure to eliminate these abnormal keratinocytes resulting in the persistence of chronic inflammation. Each of the proposed mechanisms might be a possible therapeutic target mainly by new immunomodulatory agents.
Kastelan
Marija
M
Department of Dermatovenerology, Rijeka University Hospital Center, Kresimirova 42, 51000 Rijeka, Croatia. marijakastelan@yahoo.com
Massari
Larisa Prpić
LP
Brajac
Ines
I
D017209:Apoptosis; D049109:Cell Proliferation; D006801:Humans; D015603:Keratinocytes / Q000473:pathology*; D011565:Psoriasis / Q000473:pathology*