The Potassium Channel KCNK2 is a Regulator of Immune Cell Trafficking and Inflammatory Responses in Idiopathic Inflammatory Myopathies

KCNK2, a two-pore-domain potassium channel, has been implicated as important regulator of leukocyte transmigration into the central nervous system. KCNK2-/- mice showed an increased disease severity in experimental autoimmune encephalomyelitis (animal model of multiple sclerosis). Likewise, an immune-cell infiltration can be observed as pathogenic hallmark in idiopathic-inflammatory-myopathies (IIM) as well. Therefore, we investigate if KCNK2 is involved in peripheral autoimmune responses o f IIMs. In accordance, we found KCNK2 expression in primary murine microvascular endothelial cells (PMMEC) and in primary murine muscle cells (PMMC) on gene and protein level. Stimulation with pro-inflammatory cytokines led to a downregulation of KCNK2 expression on differentiated PMMC andPMMEC. Interestingly, KCNK2-/- or pharmacological blockade of KCNK2 with spadin increased the expression of pro-inflammatory activation markers and adhesion molecules of these cells. To further elucidate the regulatory role of KCNK2, we found significantly more adhered T cells on KCNK2-/- or spadin treated PMMEC in vitro under low shear flow and in vivo in microvessels of the cremaster muscle using intravitalimaging. In summary, KCNK2 might be critically involved in the regulation of immunological processes, especially immune-cell trafficking of IIMs and might provide a deeper understanding of the regulatory mechanisms to identify new, urgently needed, therapeutic targets.