title: Kv1.3 blockers ameliorate allergic contact dermatitis by preferentially suppressing effector memory T cells in a rat model.
abstract: BACKGROUND
  The Kv1.3 voltage-gated potassium channel is selectively upregulated upon activation in effector memory T (TEM ) cells in inflamed tissue, and plays an important role in maintenance of T-cell activation. Although Kv1.3 blockers have been shown to ameliorate allergic contact dermatitis (ACD) in a rat model, it remains unknown whether the effect of Kv1.3 blockers on ACD is mediated by suppressing TEM cell function and/or whether naive T-cells or central memory T (TCM ) cells are influenced.
  
  
  OBJECTIVE
  To analyse the detailed mechanism of Kv1.3 blockers in a rat model of ACD.
  
  
  METHODS
  We examined the effects of a Kv1.3 blocker on inflammation and production of the effector cytokine interferon (IFN)-γ in inflamed tissue in rat ACD. Single-cell suspensions were isolated from inflamed rat ears (TEM cells), and regional lymph nodes (naive T/TCM cells), and the effect of Kv1.3 blockers on anti-CD3-stimulated IFN-γ production in vitro was measured.
  
  
  RESULTS
  The Kv1.3 blocker significantly suppressed ear inflammation and IFN-γ production at the protein level in vivo. It also suppressed in vitro IFN-γ production from TEM cells from inflamed tissues, but did not suppress the function of naive T/TCM cells from lymph nodes.
  
  
  CONCLUSIONS
  We found that the Kv1.3 blocker ameliorated ACD by inhibiting TEM cell functions only, thus Kv1.3 blockers could be a potentially selective therapeutic agent for TEM cell-mediated inflammatory skin diseases without producing harmful side-effects.
authors.affiliation: Innovative Drug Discovery Research Laboratories, Shionogi and Co. Ltd, Toyonaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ueyama
authors.forename: K
authors.initials: K
authors.lastname: Imura
authors.forename: E
authors.initials: E
authors.lastname: Kasai-Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Tai
authors.forename: M
authors.initials: M
authors.lastname: Nagira
authors.forename: M
authors.initials: M
authors.lastname: Shichijo
authors.forename: K
authors.initials: K
authors.lastname: Yasui
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004423:Ear; D005260:Female; D005363:Ficusin / Q000494:pharmacology*; D007156:Immunologic Memory / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: C499898:5-(4-phenylbutoxy)psoralen; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D007371:Interferon-gamma; D005363:Ficusin