Chabbert-de Ponnat Isabelle, Marie-Cardine Anne, Pasterkamp R Jeroen, Schiavon Valérie, Tamagnone Luca, Thomasset Nicole, Bensussan Armand, Boumsell Laurence
INSERM U448, Faculty of Medicine, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
Int Immunol. 2005 Apr;17(4):439-47. doi: 10.1093/intimm/dxh224. Epub 2005 Mar 3.
CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Performing competition assays, we identified plexin C1 (VESPR/CD232) as being involved in sCD100-mediated effects on human monocytes. Interestingly, we observed a complete down-regulation of plexin C1 expression during the in vitro differentiation process of monocytes to immature DCs, while concomitantly the surface expression of plexin B1 was induced. The latter receptor then binds sCD100 on immature DCs, mediating its inhibitory effect on cell migration. Finally, we showed that sCD100 modulated the cytokine production from monocytes and immature DCs. Together these results suggest that sCD100 plays a critical role in the regulation of antigen-presenting cell migration and functions via a tightly regulated process of receptor expression.
CD100是免疫系统中描述的首个信号素。它在大多数造血细胞表面以300 kDa的同二聚体形式表达，但在细胞激活后经蛋白水解切割后也以可溶性形式存在。我们在此证实，可溶性CD100（sCD100）会损害人单核细胞和未成熟树突状细胞（DC）的迁移，但不会影响成熟DC的迁移。通过进行竞争试验，我们确定丛状蛋白C1（VESPR/CD232）参与了sCD100对人单核细胞的介导作用。有趣的是，我们观察到在单核细胞体外分化为未成熟DC的过程中，丛状蛋白C1的表达完全下调，同时丛状蛋白B1的表面表达被诱导。后者受体随后与未成熟DC上的sCD100结合，介导其对细胞迁移的抑制作用。最后，我们表明sCD100调节单核细胞和未成熟DC的细胞因子产生。这些结果共同表明，sCD100通过严格调控的受体表达过程，在抗原呈递细胞迁移和功能的调节中起关键作用。
