The beneficial effect of blocking Kv1.3 in the psoriasiform SCID mouse model.
The Kv1.3 channel is important in the activation and function of effector memory T cells. Recently, specific blockers of the Kv1.3 channel have been developed as a potential therapeutic option for diverse autoimmune diseases. In psoriatic lesions, most lymphocytes are memory effector T cells. The aim of the present study was to detect the expression of Kv1.3 channels in these cells in psoriatic lesions as well as in human psoriasiform skin grafts using the severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemical staining for Kv1.3 expression and various inflammatory markers was performed in sections obtained from six psoriatic patients and 18 beige-SCID mice with psoriasiform human skin grafts. Six grafted mice were treated with Stichodactyla helianthus neurotoxin (ShK), a known Kv1.3 blocker. The results showed an increased number of Kv1.3+ cells in the psoriatic skin as well as in the psoriasiform skin grafts as compared with normal skin and normal skin grafts. Injections of ShK showed a marked therapeutic effect in three of six psoriasiform skin grafts. A significantly decreased number of Kv1.3+ cells was observed in the responders compared with the control grafts. This pilot study, although performed in a small number of mice, reveals the possible beneficial effect of Kv1.3 blockers in psoriasis patients.
Gilhar
Amos
A
Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Flieman Medical Center, Haifa, Israel. doritg_2000@yahoo.com
Bergman
Reuven
R
Assay
Bedia
B
Ullmann
Yehuda
Y
Etzioni
Amos
A
D000818:Animals; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
D003064:Cnidarian Venoms; D051664:Kv1.3 Potassium Channel; C095391:ShK neurotoxin