Barbet Gaëtan, Demion Marie, Moura Ivan C, Serafini Nicolas, Léger Thibaut, Vrtovsnik François, Monteiro Renato C, Guinamard Romain, Kinet Jean-Pierre, Launay Pierre
Institut National de la Santé et de la Recherche Médicale U699, Paris, France.
Nat Immunol. 2008 Oct;9(10):1148-56. doi: 10.1038/ni.1648. Epub 2008 Aug 31.
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 (Ca(2+)) entry governs the functions of many hematopoietic cell types, but the role of Ca(2+) entry in DC biology remains unclear. Here we report that the Ca(2+)-activated nonselective cation channel TRPM4 was expressed in and controlled the Ca(2+) homeostasis of mouse DCs. The absence of TRPM4, which elicited Ca(2+) overload, did not influence DC maturation but did considerably impair chemokine-dependent DC migration. Our results establish TRPM4-regulated Ca(2+) homeostasis as crucial for DC mobility but not maturation and emphasize that DC maturation and migration are independently regulated.
树突状细胞(DC)的成熟和迁移是启动免疫反应的关键事件。遇到病原体后,DC上调共刺激分子的表达,随后迁移至次级淋巴器官。钙离子(Ca(2+))内流控制着许多造血细胞类型的功能,但Ca(2+)内流在DC生物学中的作用仍不清楚。在此,我们报告Ca(2+)激活的非选择性阳离子通道TRPM4在小鼠DC中表达并控制其Ca(2+)稳态。缺乏TRPM4会引发Ca(2+)过载,这并不影响DC的成熟,但会显著损害趋化因子依赖性DC迁移。我们的结果表明,TRPM4调节的Ca(2+)稳态对DC的迁移至关重要,但对其成熟并非如此,并强调DC的成熟和迁移是独立调节的。