Faure-André Gabrielle, Vargas Pablo, Yuseff Maria-Isabel, Heuzé Mélina, Diaz Jheimmy, Lankar Danielle, Steri Veronica, Manry Jeremy, Hugues Stéphanie, Vascotto Fulvia, Boulanger Jérôme, Raposo Graça, Bono Maria-Rosa, Rosemblatt Mario, Piel Matthieu, Lennon-Duménil Ana-Maria
INSERM U653, Institut Curie, 12 rue Lhomond, 75005, Paris, France.
Science. 2008 Dec 12;322(5908):1705-10. doi: 10.1126/science.1159894.
Dendritic cells (DCs) sample peripheral tissues of the body in search of antigens to present to T cells. This requires two processes, antigen processing and cell motility, originally thought to occur independently. We found that the major histocompatibility complex II-associated invariant chain (Ii or CD74), a known regulator of antigen processing, negatively regulates DC motility in vivo. By using microfabricated channels to mimic the confined environment of peripheral tissues, we found that wild-type DCs alternate between high and low motility, whereas Ii-deficient cells moved in a faster and more uniform manner. The regulation of cell motility by Ii depended on the actin-based motor protein myosin II. Coupling antigen processing and cell motility may enable DCs to more efficiently detect and process antigens within a defined space.
树突状细胞(DCs)对身体外周组织进行采样,以寻找抗原呈递给T细胞。这需要两个过程,即抗原加工和细胞运动,最初认为这两个过程是独立发生的。我们发现,主要组织相容性复合体II相关恒定链(Ii或CD74),一种已知的抗原加工调节因子,在体内对DC运动具有负调节作用。通过使用微制造通道模拟外周组织的受限环境,我们发现野生型DC在高运动性和低运动性之间交替,而Ii缺陷型细胞以更快且更均匀的方式移动。Ii对细胞运动的调节依赖于基于肌动蛋白的运动蛋白肌球蛋白II。将抗原加工与细胞运动耦合起来,可能使DC能够在限定空间内更有效地检测和加工抗原。