Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells

Abstract

The two-pore domain K⁺ channel K_2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K_2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4⁺ T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 μM) markedly decreased full-length K_2P5.1 transcription in activated CD4⁺ T cells, resulting in the disappearance of K_2P5.1 activity and an imbalance in Th17 and T_reg cytokines. These results suggest that the defect in K_2P5.1 splicing by the pre-mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine production in K_2P5.1-associated autoimmune diseases.

Keywords: K(+) channel; K(2P)5.1; Pre-mRNA splicing inhibitor.