Conflict of interest: none declared.
Experimental dermatology ● Original article
Kv1.3 blockers ameliorate allergic contact dermatitis by preferentially suppressing effector memory T cells in a rat model
Version of Record online: 20 NOV 2013
© 2013 British Association of Dermatologists
Clinical and Experimental Dermatology
Volume 38, Issue 8, pages 897–903, December 2013
How to Cite
Ueyama, A., Imura, K., Kasai-Yamamoto, E., Tai, N., Nagira, M., Shichijo, M. and Yasui, K. (2013), Kv1.3 blockers ameliorate allergic contact dermatitis by preferentially suppressing effector memory T cells in a rat model. Clinical and Experimental Dermatology, 38: 897–903. doi: 10.1111/ced.12097
- Issue online: 20 NOV 2013
- Version of Record online: 20 NOV 2013
- Manuscript Accepted: 9 OCT 2012
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.
To analyse the detailed mechanism of Kv1.3 blockers in a rat model of ACD.
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.
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.
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.