Defective splicing of the background K channel K5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4 T cells.

The two-pore domain K channel K5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K5.1 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 K5.1 transcription in activated CD4 T cells, resulting in the disappearance of K5.1 activity and an imbalance in Th17 and T cytokines. These results suggest that the defect in K5.1 splicing by the pre-mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine production in K5.1-associated autoimmune diseases.