Immature human dendritic cells enhance their migration through KCa3.1 channel activation

Cell Calcium. 2016 Apr;59(4):198-207. doi: 10.1016/j.ceca.2016.02.008. Epub 2016 Mar 4.

Abstract

Migration capacity is essential for dendritic cells (DCs) to present antigen to T cells for the induction of immune response. The DC migration is supposed to be a calcium-dependent process, while not fully understood. Here, we report a role of the KCa3.1/IK1/SK4 channels in the migration capacity of both immature (iDC) and mature (mDC) human CD14(+)-derived DCs. KCa3.1 channels were shown to control the membrane potential of human DC and the Ca(2+) entry, which is directly related to migration capacities. The expression of migration marker such as CCR5 and CCR7 was modified in both types of DCs by TRAM-34 (100nM). But, only the migration of iDC was decreased by use of both TRAM-34 and KCa3.1 siRNA. Confocal analyses showed a close localization of CCR5 with KCa3.1 in the steady state of iDC. Finally, the implication of KCa3.1 seems to be limited to the migration capacities as T cell activation of DCs appeared unchanged. Altogether, these results demonstrated that KCa3.1 channels have a pro-migratory effect on iDC migration. Our findings suggest that KCa3.1 in human iDC play a major role in their migration and constitute an attractive target for the cell therapy optimization.

Keywords: Dendritic cell; Human; KCa3.1/SK4/IK1; Migration.

MeSH terms

  • Calcium / metabolism*
  • Cell Movement* / drug effects
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Pyrazoles / pharmacology

Substances

  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human
  • Pyrazoles
  • TRAM 34
  • Calcium