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K v1.3 blockers ameliorate allergic contact dermatitis by preferentially suppressing effector memory T cells in a rat model
Author(s) -
Ueyama A.,
Imura K.,
KasaiYamamoto E.,
Tai N.,
Nagira M.,
Shichijo M.,
Yasui K.
Publication year - 2013
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12097
Subject(s) - effector , allergic contact dermatitis , contact dermatitis , medicine , immunology , allergy
Summary Background The K v1.3 voltage‐gated potassium channel is selectively upregulated upon activation in effector memory T ( T EM ) cells in inflamed tissue, and plays an important role in maintenance of T ‐cell activation. Although K v1.3 blockers have been shown to ameliorate allergic contact dermatitis ( ACD ) in a rat model, it remains unknown whether the effect of K v1.3 blockers on ACD is mediated by suppressing T EM cell function and/or whether naive T ‐cells or central memory T ( T CM ) cells are influenced. Aim To analyse the detailed mechanism of K v1.3 blockers in a rat model of ACD . Methods We examined the effects of a K v1.3 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 ( T EM cells), and regional lymph nodes (naive T / T CM cells), and the effect of K v1.3 blockers on anti‐ CD 3‐stimulated IFN ‐γ production in vitro was measured. Results The K v1.3 blocker significantly suppressed ear inflammation and IFN ‐γ production at the protein level in vivo . It also suppressed in vitro IFN ‐γ production from T EM cells from inflamed tissues, but did not suppress the function of naive T / T CM cells from lymph nodes. Conclusions We found that the K v1.3 blocker ameliorated ACD by inhibiting T EM cell functions only, thus K v1.3 blockers could be a potentially selective therapeutic agent for T EM cell‐mediated inflammatory skin diseases without producing harmful side‐effects.