Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking
Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking
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DOI：
10.1038/ni1111
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发表时间：
2004-10-01
影响因子：
30.5
通讯作者：
Kinashi, T
中科院分区：
文献类型：
--
作者：
Katagiri, K;Ohnishi, N;Kinashi, T
免疫监视需要趋化因子和粘附分子的协调调节来引导免疫细胞迁移。然而，控制免疫细胞高运输能力的关键分子尚不清楚。在这里，我们表明，效应分子RAPL是不可缺少的整合素介导的粘附和迁移的淋巴细胞和树突状细胞。RAPL缺陷导致缺陷的趋化因子触发的淋巴细胞粘附和迁移到次级淋巴器官，导致萎缩的淋巴滤泡和缺陷的边缘区B细胞，伴随着血液中未成熟的B细胞增加。此外，脾脏树突状细胞减少，粘附缺陷。在被炎症刺激激活后，皮肤和脾脏树突状细胞不能迁移到引流淋巴结或脾脏的白色髓中。因此，RAPL是免疫监视所必需的关键免疫细胞运输调节剂。
Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule for governing the high trafficking capability of immune cells is not clear. Here we show that the effector molecule RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency caused defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. After being activated with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance.