Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively
Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively
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DOI：
10.1093/intimm/dxh224
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Boumsell, L
中科院分区：
文献类型：
--
作者：
Chabbert-de Ponnat, I;Marie-Cardine, A;Boumsell, L
CD100是免疫系统中描述的第一个信号蛋白。它在大多数造血细胞表面以300 kda的同型二聚体表达，但也在细胞活化后的蛋白水解裂解后以可溶性形式存在。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（DCs）的迁移，但不会损害成熟树突状细胞（DCs）。通过竞争分析，我们发现丛蛋白C1 （VESPR/CD232）参与了scd100介导的对人类单核细胞的影响。有趣的是，在单核细胞向未成熟dc的体外分化过程中，我们观察到丛蛋白C1的表达完全下调，同时丛蛋白B1的表面表达也被诱导。后一受体随后在未成熟的dc上结合sCD100，介导其对细胞迁移的抑制作用。最后，我们发现sCD100调节单核细胞和未成熟dc的细胞因子产生。综上所述，这些结果表明sCD100在抗原呈递细胞迁移的调控中起着关键作用，并通过一个严格调控的受体表达过程发挥作用。
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.