Altered calcium influx of peripheral Th2 cells in pediatric Crohn's disease: infliximab may normalize activation patterns

Abstract

ObjectiveCrohn's disease is a chronic inflammation of the gastrointestinal tract with an abnormal immune phenotype. We investigated how intracellular calcium kinetics of Th1 and Th2 lymphocytes alter upon specific inhibition of Kv1.3 and IKCa1 channels in pediatric Crohn's disease.Study designBlood was taken from 12 healthy and 29 Crohn's disease children. Of those, 6 were switched to infliximab and re-sampled after the 4th infliximab treatment. Intracellular calcium levels were monitored using flow cytometry in the presence or absence of specific inhibitors of Kv1.3 and IKCa1 potassium channels.ResultsIn Crohn's disease treated with standard therapy, calcium response during activation was higher than normal in Th2 cells. This was normalized in vitro by inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab, potassium channel function and expression in Th2 lymphocytes were comparable to those in Th1 cells.ConclusionThese results may indicate that potassium channels are potential immune modulatory targets in Crohn's disease.

KCNN4 Expression Is Elevated in Inflammatory Bowel Disease: This Might Be a Novel Marker and Therapeutic Option Targeting Potassium Channels

“…T cell activation is altered by the expression level and activity of KCNN4 in T lymphocytes in pediatric patients with IBD [51]. The expression level of KCNN4 can be restored by anti-TNF therapy in these patients [52]. KCNN4 expression in T cells can be correlated with disease activity in UC [48].…”

Biological Treatments in Inflammatory Bowel Disease: A Complex Mix of Mechanisms and Actions

“…Beyond these modulatory changes on cell populations, the impact of anti-TNF-α on cell adhesion molecules and angiogenesis has also been examined [94,97,100], as well as their role in gut barrier function [91,93], and calcium influx and potassium channels [102,103]. These studies provide additional mechanistic basis for anti-TNF-α antibodies, although it should be noted that they have been studied to a lower extent compared with the aforementioned mechanisms [104].…”