The two-pore domain K+ channel K(2P)5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K(2P)5.1 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 mu M) markedly decreased full-length K(2P)5.1 transcription in activated CD4(+) T cells, resulting in the disappearance of K(2P)5.1 activity and an imbalance in Th17 and T-reg cytokines. These results suggest that the defect in K(2P)5.1 splicing by the pre-mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine production in K(2P)5.1-associated autoimmune diseases. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).