Van Vu Quang, Lesage Sylvie, Bouguermouh Salim, Gautier Patrick, Rubio Manuel, Levesque Martin, Nguyen Sébastien, Galibert Laurent, Sarfati Marika
Immunoregulation Laboratory, CHUM Research Center, University of Montreal, Montreal, Quebec, Canada.
EMBO J. 2006 Nov 29;25(23):5560-8. doi: 10.1038/sj.emboj.7601415. Epub 2006 Nov 9.
Dendritic cells (DCs) capture and process Ag in the periphery. Thus, traffic through lymphatic vessels is mandatory before DCs relocate to lymph nodes where they are dedicated to T-cell priming. Here, we show that the ubiquitous self-marker CD47 selectively regulates DC, but not T and B cell trafficking across lymphatic vessels and endothelial barriers in vivo. We find an altered skin DC migration and impaired T-cell priming in CD47-deficient mice at steady state and under inflammatory conditions. Competitive DC migration assays and active immunization with myeloid DCs demonstrate that CD47 expression is required on DCs but not on the endothelium for efficient DC trafficking and T-cell responses. This migratory defect correlates with the quasi-disappearance of splenic marginal zone DCs in nonmanipulated CD47-deficient mice. Nonetheless, CCR7 expression and CCL19-driven chemotaxis remain intact. Our data reveal that CD47 on DCs is a critical factor in controlling migration and efficient initiation of the immune response.
树突状细胞（DCs）在外周捕获并处理抗原。因此，在DCs迁移至淋巴结致力于启动T细胞之前，通过淋巴管运输是必不可少的。在此，我们表明普遍存在的自身标志物CD47在体内选择性调节DCs穿过淋巴管和内皮屏障的运输，但不调节T细胞和B细胞的运输。我们发现在稳态和炎症条件下，CD47缺陷小鼠的皮肤DC迁移改变且T细胞启动受损。竞争性DC迁移试验和用髓样DC进行主动免疫表明，为了实现高效的DC运输和T细胞反应，DCs上需要有CD47表达，而内皮细胞上则不需要。这种迁移缺陷与未处理的CD47缺陷小鼠脾脏边缘区DCs的近乎消失有关。尽管如此，CCR7表达和CCL19驱动的趋化性仍然完好无损。我们的数据表明，DCs上的CD47是控制免疫反应迁移和有效启动的关键因素。
