Kv1.3 blockers ameliorate allergic contact dermatitis by preferentially suppressing effector memory T cells in a rat model

Clin Exp Dermatol. 2013 Dec;38(8):897-903. doi: 10.1111/ced.12097.

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.

Aim: 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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dermatitis, Allergic Contact / drug therapy*
  • Dermatitis, Allergic Contact / immunology
  • Dermatitis, Allergic Contact / metabolism
  • Disease Models, Animal
  • Ear
  • Female
  • Ficusin / pharmacology*
  • Immunologic Memory / drug effects*
  • Interferon-gamma / metabolism
  • Kv1.3 Potassium Channel / antagonists & inhibitors*
  • Kv1.3 Potassium Channel / physiology
  • Lymph Nodes / cytology
  • Potassium Channel Blockers / pharmacology*
  • Rats
  • T-Lymphocytes / drug effects*

Substances

  • 5-(4-phenylbutoxy)psoralen
  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers
  • Interferon-gamma
  • Ficusin