title: Immature human dendritic cells enhance their migration through KCa3.1 channel activation.
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.
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: David
authors.initials: D
authors.lastname: Crottès
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Félix
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Meley
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chadet
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Herr
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Audiger
authors.affiliation: Institut de Biologie Valrose (iBV), CNRS UMR7277, Inserm U1091, UNS 28, Avenue Valrose, 06108 Nice, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Soriani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1069, Université François-Rabelais de Tours, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vandier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1069, Université François-Rabelais de Tours, 10 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roger
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France; Service de cardiologie, CHRU de Tours, 2 Bd Tonnellé, F-37032 Tours, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.affiliation: EA 4245Cellules Dendritiques, Immuno-modulation et Greffes, Université François-Rabelais de Tours, UFR de Médecine, 10 Bd Tonnellé, F-37032 Tours, France; UFR des Sciences Pharmaceutiques, Av Monge, F-37000 Tours, France. Electronic address: florence.velge-roussel@univ-tours.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Velge-Roussel
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D011720:Pyrazoles; C411671:TRAM 34; D002118:Calcium
keywords: Dendritic cell; Human; KCa3.1/SK4/IK1; Migration