Article abstract
Nature Immunology 9, 1148 - 1156 (2008)
Published online: 31 August 2008 | doi:10.1038/ni.1648
The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells
Gaëtan Barbet1,2,3,7, Marie Demion1,2,3,7, Ivan C Moura1,3,7, Nicolas Serafini1,2,3, Thibaut Léger1,2,3, François Vrtovsnik1,3,4, Renato C Monteiro1,3, Romain Guinamard5, Jean-Pierre Kinet6 & Pierre Launay1,2,3
Abstract
Dendritic cell (DC) maturation and migration are events critical for the initiation of immune responses. After encountering pathogens, DCs upregulate the expression of costimulatory molecules and subsequently migrate to secondary lymphoid organs. Calcium (Ca2+) entry governs the functions of many hematopoietic cell types, but the role of Ca2+ entry in DC biology remains unclear. Here we report that the Ca2+-activated nonselective cation channel TRPM4 was expressed in and controlled the Ca2+ homeostasis of mouse DCs. The absence of TRPM4, which elicited Ca2+ overload, did not influence DC maturation but did considerably impair chemokine-dependent DC migration. Our results establish TRPM4-regulated Ca2+ homeostasis as crucial for DC mobility but not maturation and emphasize that DC maturation and migration are independently regulated.
- Institut National de la Santé et de la Recherche Médicale U699, Paris F-75018, France.
- Equipe Avenir, Institut National de la Santé et de la Recherche Médicale, Paris F-75018, France.
- Université Paris 7-Denis Diderot, Faculté de Médecine, Site Xavier Bichat, Paris F-75018, France.
- Hôpital Bichat, Service de Néphrologie, Paris F-75018, France.
- Laboratoire de Physiologie Cellulaire, EA 3212, Université de Caen, Caen, F-14032, France.
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
- These authors contributed equally to this work.
Correspondence to: Pierre Launay1,2,3 e-mail: pierre.launay@inserm.fr
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